Herbal interactions with anticancer drugs: Mechanistic and clinical considerations

Current Medicinal Chemistry

Volumn 17, Issue 16, 2010, Pages 1635-1678

  Yang, An Kui ^a,b   He, Shu Ming ^c   Liu, Liang ^d   Liu, Jun Ping ^e   Wei, Ming Qian ^f   Zhou, Shu Feng ^g  

^a SUN YAT SEN UNIVERSITY   (China)

^b SUN YAT SEN UNIVERSITY CANCER CENTER   (China)

^c Xiaolan People's Hospital Affiliated to Nanfang Medical University   (China)

^d HONG KONG BAPTIST UNIVERSITY   (Hong Kong)

^e MONASH UNIVERSITY   (Australia)

^f GRIFFITH UNIVERSITY   (Australia)

^g RMIT UNIVERSITY   (Australia)

Author keywords

Anticancer drug; Cytochrome p450; Drug resistance; Herb drug interaction; Herbal medicine; P glycoprotein; Pharmacokinetics; St john's wort; Toxicity

Indexed keywords

7 ETHYL 10 HYDROXYCAMPTOTHECIN; AJOENE; ALLICIN; ALLIIN; ANTHRAQUINONE DERIVATIVE; ANTINEOPLASTIC AGENT; ASTRAGALOSIDE IV; BREAST CANCER RESISTANCE PROTEIN; CARRIER PROTEIN; CURCUMIN; DIALLYL TRISULFIDE; DOCETAXEL; GARLIC EXTRACT; GINGEROL; GINSENG EXTRACT; GINSENOSIDE; GLYCOPROTEIN P; HERBACEOUS AGENT; HYPERICUM PERFORATUM EXTRACT; IMATINIB; IRINOTECAN; MULTIDRUG RESISTANCE PROTEIN; ORGANOSULFUR DERIVATIVE; POLYSACCHARIDE; SAPONIN DERIVATIVE; SHOGAOL; TANNIN; TANSHINONE; TERPENOID DERIVATIVE; UNINDEXED DRUG;

ARTICLE; BREAST CANCER; CANCER GROWTH; DRUG METABOLISM; GARLIC; HERBAL MEDICINE; HUMAN; HYPERICUM PERFORATUM; NONHUMAN; TALUS; TREATMENT DURATION; VISCUM ALBUM;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUGS, CHINESE HERBAL; ENZYMES; GENE EXPRESSION REGULATION, NEOPLASTIC; HERB-DRUG INTERACTIONS; HUMANS; NEOPLASMS;

EID: 77953528461     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986710791111279     Document Type: Article

References (439)

1. Parkin, D.M.; Bray, F.; Ferlay, J.; Pisani, P. Global cancer statistics, 2002. CA Cancer J. Clin., 2005, 55, 74-108.
2. Gatenby, R.A. A change of strategy in the war on cancer. Nature,2009, 459, 508-509.
3. Chabner, B.A.; Roberts, T.G., Jr. Timeline: Chemotherapy and thewar on cancer. Nat. Rev. Cancer, 2005, 5, 65-72.
4. Cotter, T.G. Apoptosis and cancer: the genesis of a research field. Nat. Rev. Cancer, 2009, 9, 501-507.
5. Undevia, S.D.; Gomez-Abuin, G.; Ratain, M.J. Pharmacokineticvariability of anticancer agents. Nat. Rev. Cancer, 2005, 5, 447-458.
6. Yague, E.; Raguz, S. Drug resistance in cancer. Br. J. Cancer,2005, 93, 973-976.
7. Engdal, S.; Klepp, O.; Nilsen, O.G. Identification and explorationof herbdrug combinations used by cancer patients. Integr. CancerTher., 2009, 8, 29-36.
8. Ernst, E.; Cassileth, B.R. The prevalence of complementary/alternative medicine in cancer: a systematic review. Cancer,1998, 83, 777-782.
9. Sparreboom, A.; Cox, M.C.; Acharya, M.R.; Figg, W.D. Herbalremedies in the United States: potential adverse interactions withanticancer agents. J. Clin. Oncol., 2004, 22, 2489-2503.
10. Warshafsky, S.; Kamer, R.S.; Sivak, S.L. Effect of garlic on totalserum cholesterol. A meta-analysis. Ann. Intern. Med., 1993, 119,599-605.
11. Werneke, U.; Earl, J.; Seydel, C.; Horn, O.; Crichton, P.; Fannon, D. Potential health risks of complementary alternative medicines incancer patients. Br. J. Cancer, 2004, 90, 408-413.
12. MacLennan, A.H.; Wilson, D.H.; Taylor, A.W. The escalating costand prevalence of alternative medicine. Prev. Med., 2002, 35, 166-173.
13. Hu, Z.; Yang, X.; Ho, P.C.; Chan, S.Y.; Heng, P.W.; Chan, E.; Duan, W.; Koh, H.L.; Zhou, S. Herb-drug interactions: a literaturereview. Drugs, 2005, 65, 1239-1282.
14. Izzo, A.A. Herb-drug interactions: an overview of the clinical evidence. Fundam. Clin. Pharmacol., 2005, 19, 1-16.
15. Ernst, E. The role of complementary and alternative medicine incancer. Lancet Oncol., 2000, 1, 176-180.
16. Gratus, C.; Wilson, S.; Greenfield, S.M.; Damery, S.L.; Warmington, S.A.; Grieve, R.; Steven, N.M.; Routledge, P. The use ofherbal medicines by people with cancer: a qualitative study. BMC Complement. Altern. Med., 2009, 9, 14.
17. Girgis, A.; Adams, J.; Sibbritt, D. The use of complementary andalternative therapies by patients with cancer. Oncol. Res., 2005, 15,281-289.
18. Block, K.I.; Gyllenhaal, C.; Mead, M.N. Safety and efficacy ofherbal sedatives in cancer care. Integr. Cancer Ther., 2004, 3, 128-148.
19. Ho, J.W.; Jie, M. Pharmacological activity of cardiovascular agentsfrom herbal medicine. Cardiovasc. Hematol. Agents Med. Chem.,2007, 5, 273-277.
20. Chu, D.T.; Wong, W.L.; Mavligit, G.M. Immunotherapy withChinese medicinal herbs. I. Immune restoration of local xenogeneicgraft-versus-host reaction in cancer patients by fractionated Astragalus membranaceus in vitro. J. Clin. Lab. Immunol., 1988, 25,119-123.
21. Taixiang, W.; Munro, A.J.; Guanjian, L. Chinese medical herbs forchemotherapy side effects in colorectal cancer patients. Cochrane Database Syst. Rev., 2005, CD004540.
22. McCulloch, M.; See, C.; Shu, X.J.; Broffman, M.; Kramer, A.; Fan, W.Y.; Gao, J.; Lieb, W.; Shieh, K.; Colford, J.M., Jr. Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomizedtrials. J. Clin. Oncol., 2006, 24, 419-430.
23. Cassileth, B.R.; Rizvi, N.; Deng, G.; Yeung, K.S.; Vickers, A.; Guillen, S.; Woo, D.; Coleton, M.; Kris, M.G. Safety and pharmacokinetic trial of docetaxel plus an Astragalus-based herbal formulafor non-small cell lung cancer patients. Cancer Chemother. Pharmacol., 2009, 65, 67-71.
24. Ma, W.H.; Duan, K.N.; Feng, M.; She, B.; Chen, Y.; Zhang, R.M. [Aidi Injection as an adjunct therapy for non-small cell lung cancer:a systematic review]. Zhong Xi Yi Jie He Xue Bao, 2009, 7, 315-324.
25. Gonzales, G.F.; Valerio, L.G., Jr. Medicinal plants from Peru: areview of plants as potential agents against cancer. Anticancer Agents Med. Chem., 2006, 6, 429-444.
26. Amaral, S.; Mira, L.; Nogueira, J.M.; da Silva, A.P.; Helena Florencio, M. Plant extracts with anti-inflammatory properties a newapproach for characterization of their bioactive compounds and establishment of structure-antioxidant activity relationships. Bioorg.Med. Chem., 2009, 17, 1876-1883.
27. Riva, L.; Coradini, D.; Di Fronzo, G.; De Feo, V.; De Tommasi,N.; De Simone, F.; Pizza, C. The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line. Anticancer Res., 2001, 21, 2457-2461.
28. Bacher, N.; Tiefenthaler, M.; Sturm, S.; Stuppner, H.; Ausserlechner, M.J.; Kofler, R.; Konwalinka, G. Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrestedand bcl-2-expressing acute lymphoblastic leukaemia cells. Br. J.Haematol., 2006, 132, 615-622.
29. Cheng, A.C.; Jian, C.B.; Huang, Y.T.; Lai, C.S.; Hsu, P.C.; Pan, M.H. Induction of apoptosis by Uncaria tomentosa through reactive oxygen species production, cytochrome c release, and caspasesactivation in human leukemia cells. Food Chem. Toxicol., 2007, 45,2206-2218.
30. Pilarski, R.; Poczekaj-Kostrzewska, M.; Ciesiolka, D.; Szyfter, K.; Gulewicz, K. Antiproliferative activity of various Uncaria tomentosa preparations on HL-60 promyelocytic leukemia cells. Pharmacol. Rep., 2007, 59, 565-572.
31. Mok, T.; Yeo, W.; Johnson, P.; Hui, P.; Ho, W.; Lam, K.; Xu, M.; Chak, K.; Chan, A.; Wong, H.; Mo, F.; Zee, B. A double-blind placebo-controlled randomized study of Chinese herbal medicine ascomplementary therapy for reduction of chemotherapy-inducedtoxicity. Ann. Oncol., 2007, 18, 768-774.
32. Molassiotis, A.; Potrata, B.; Cheng, K.K. A systematic review ofthe effectiveness of Chinese herbal medication in symptom management and improvement of quality of life in adult cancer patients. Complement. Ther. Med., 2009, 17, 92-120.
33. Sharma, R.A.; Gescher, A.J.; Steward, W.P. Curcumin: the story sofar. Eur. J. Cancer, 2005, 41, 1955-1968.
34. Anand, P.; Thomas, S.G.; Kunnumakkara, A.B.; Sundaram, C.; Harikumar, K.B.; Sung, B.; Tharakan, S.T.; Misra, K.; Priyadarsini, I.K.; Rajasekharan, K.N.; Aggarwal, B.B. Biological activities ofcurcumin and its analogues (Congeners) made by man and MotherNature. Biochem. Pharmacol., 2008, 76, 1590-1611.
35. Wang, Y.J.; Pan, M.H.; Cheng, A.L.; Lin, L.I.; Ho, Y.S.; Hsieh, C.Y.; Lin, J.K. Stability of curcumin in buffer solutions and characterization of its degradation products. J. Pharm. Biomed. Anal.,1997, 15, 1867-1876.
36. Begum, A.N.; Jones, M.R.; Lim, G.P.; Morihara, T.; Kim, P.; Heath, D.D.; Rock, C.L.; Pruitt, M.A.; Yang, F.; Hudspeth, B.; Hu, S.; Faull, K.F.; Teter, B.; Cole, G.M.; Frautschy, S.A. Curcuminstructure-function, bioavailability, and efficacy in models of neu-roinflammation and Alzheimer's disease. J. Pharmacol. Exp. Ther.,2008, 326, 196-208.
37. Garcea, G.; Jones, D.J.; Singh, R.; Dennison, A.R.; Farmer, P.B.; Sharma, R.A.; Steward, W.P.; Gescher, A.J.; Berry, D.P. Detectionof curcumin and its metabolites in hepatic tissue and portal bloodof patients following oral administration. Br. J. Cancer, 2004, 90,1011-1015.
38. Ireson, C.; Orr, S.; Jones, D.J.; Verschoyle, R.; Lim, C.K.; Luo, J.L.; Howells, L.; Plummer, S.; Jukes, R.; Williams, M.; Steward, W.P.; Gescher, A. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in therat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res., 2001, 61, 1058-1064.
39. Tamvakopoulos, C.; Dimas, K.; Sofianos, Z.D.; Hatziantoniou, S.; Han, Z.; Liu, Z.L.; Wyche, J.H.; Pantazis, P. Metabolism and anticancer activity of the curcumin analogue, dimethoxycurcumin. Clin. Cancer Res., 2007, 13, 1269-1277.
40. Sakano, K.; Kawanishi, S. Met-aletal/et-al-mediated DNA damage inducedby curcumin in the presence of human cytochrome P450 isozymes.Arch. Biochem. Biophys., 2002, 405, 223-230.
41. Hsu, C.H.; Cheng, A.L. Clinical studies with curcumin. Adv. Exp.Med. Biol., 2007, 595, 471-480.
42. Sharma, R.A.; Steward, W.P.; Gescher, A.J. Pharmacokinetics andpharmacodynamics of curcumin. Adv. Exp. Med. Biol., 2007, 595,453-470.
43. Sharma, R.A.; Euden, S.A.; Platton, S.L.; Cooke, D.N.; Shafayat, A.; Hewitt, H.R.; Marczylo, T.H.; Morgan, B.; Hemingway, D.; Plummer, S.M.; Pirmohamed, M.; Gescher, A.J.; Steward, W.P. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin. Cancer Res., 2004, 10, 6847-6854.
44. Dhillon, N.; Aggarwal, B.B.; Newman, R.A.; Wolff, R.A.; Kun-numakkara, A.B.; Abbruzzese, J.L.; Ng, C.S.; Badmaev, V.; Kurzrock, R. Phase II trial of curcumin in patients with advancedpancreatic cancer. Clin. Cancer Res., 2008, 14, 4491-4499.
45. Somasundaram, S.; Edmund, N.A.; Moore, D.T.; Small, G.W.; Shi, Y.Y.; Orlowski, R.Z. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res.,2002, 62, 3868-3875.
46. Wu, B.; Liu, M.; Zhang, S. Dan Shen agents for acute ischaemicstroke. Cochrane Database Syst. Rev., 2004, CD004295.
47. Zhou, L.; Zuo, Z.; Chow, M.S. Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J. Clin. Pharmacol., 2005, 45, 1345-1359.
48. Gu, M.; Zhang, G.; Su, Z.; Ouyang, F. Identification of major active constituents in the fingerprint of Salvia miltiorrhiza Bunge developed by high-speed counter-current chromatography. J. Chro-matogr. A, 2004, 1041, 239-243.
49. Lay, I.S.; Chiu, J.H.; Shiao, M.S.; Lui, W.Y.; Wu, C.W. Crudeextract of Salvia miltiorrhiza and salvianolic acid B enhance in vi-tro angiogenesis in murine SVR endothelial cell line. Planta Med.,2003, 69, 26-32.
50. Liu, J.; Shen, H.M.; Ong, C.N. Role of intracellular thiol depletion,mitochondrial dysfunction and reactive oxygen species in Salviamiltiorrhiza-induced apoptosis in human hepatoma HepG2 cells. Life Sci., 2001, 69, 1833-1850.
51. Wu, W.L.; Chang, W.L.; Chen, C.F. Cytotoxic activities of tanshi-nones against human carcinoma cell lines. Am. J. Chin. Med., 1991,19, 207-216.
52. Zhang, J.; Huang, M.; Guan, S.; Bi, H.C.; Pan, Y.; Duan, W.; Chan, S.Y.; Chen, X.; Hong, Y.H.; Bian, J.S.; Yang, H.Y.; Zhou, S. A mechanistic study of the intestinal absorption of cryptotanshinone, the major active constituent of Salvia miltiorrhiza. J. Pharmacol. Exp. Ther., 2006, 317, 1285-1294.
53. Yu, X.Y.; Lin, S.G.; Zhou, Z.W.; Chen, X.; Liang, J.; Liu, P.Q.; Duan, W.; Chowbay, B.; Wen, J.Y.; Li, C.G.; Zhou, S.F. Role of P-glycoprotein in the intestinal absorption of tanshinone IIA, a majoractive ingredient in the root of Salvia miltiorrhiza Bunge. Curr.Drug Metab., 2007, 8, 325-340.
54. Yu, X.Y.; Zhou, Z.W.; Lin, S.G.; Chen, X.; Yu, X.Q.; Liang, J.; Duan, W.; Wen, J.Y.; Li, X.T.; Zhou, S.F. Role of ATP-bindingcassette drug transporters in the intestinal absorption of tanshinoneIIB, one of the major active diterpenoids from the root of Salviamiltiorrhiza. Xenobiotica, 2007, 37, 375-415.
55. Yu, X.Y.; Lin, S.G.; Chen, X.; Zhou, Z.W.; Liang, J.; Duan, W.; Chowbay, B.; Wen, J.Y.; Chan, E.; Cao, J.; Li, C.G.; Zhou, S.F. Transport of cryptotanshinone, a major active triterpenoid in Salviamiltiorrhiza bunge widely used in the treatment of stroke and Alzheimer's disease, across the blood-brain barrier. Curr. Drug Metab.,2007, 8, 365-378.
56. Hao, H.; Wang, G.; Cui, N.; Li, J.; Xie, L.; Ding, Z. Pharmacokinetics, absorption and tissue distribution of tanshinone IIA soliddispersion. Planta Med., 2006, 72, 1311-1317.
57. Qiu, F.; Zhang, R.; Sun, J.; Jiye, A.; Hao, H.; Peng, Y.; Ai, H.; Wang, G. Inhibitory effects of seven components of danshen extract on catalytic activity of cytochrome P450 enzyme in humanliver microsomes. Drug Metab. Dispos., 2008, 36, 1308-1314.
58. Izzat, M.B.; Yim, A.P.C.; El-Zufari, M.H. A taste of Chinese medicine! Ann. Thorac. Surg., 1998, 66, 941-942.
59. Tamayo, C.; Richardson, M.A.; Diamond, S.; Skoda, I. The chemistry and biological activity of herbs used in Flor-Essence herbaltonic and Essiac. Phytother. Res., 2000, 14, 1-14.
60. Dy, G.K.; Bekele, L.; Hanson, L.J.; Furth, A.; Mandrekar, S.; Sloan, J.A.; Adjei, A.A. Complementary and alternative medicineuse by patients enrolled onto Phase I clinical trials. J. Clin. Oncol.,2004, 22, 4810-4815.
61. Tai, J.; Cheung, S. In vitro culture studies of Flor Essence on humantumor cell lines. Phytother. Res., 2005, 19, 107-112.
62. Leonard, S.S.; Keil, D.; Mehlman, T.; Proper, S.; Shi, X.; Harris, G.K. Essiac tea: scavenging of reactive oxygen species and effectson DNA damage. J. Ethnopharmacol., 2006, 103, 288-296.
63. Al-Sukhni, W.; Grunbaum, A.; Fleshner, N. Remission of hor-mone-refractory prostate cancer attributed to Essiac. Can. J. Urol.,2005, 12, 2841-2842.
64. Zick, S.M.; Sen, A.; Feng, Y.; Green, J.; Olatunde, S.; Boon, H. Trial of Essiac to ascertain its effect in women with breast cancer(TEA-BC). J. Altern. Complement. Med., 2006, 12, 971-980.
65. Kulp, K.S.; Montgomery, J.L.; Nelson, D.O.; Cutter, B.; Latham, E.R.; Shattuck, D.L.; Klotz, D.M.; Bennett, L.M. Essiac and Flor-Essence herbal tonics stimulate the in vitro growth of human breastcancer cells. Breast Cancer Res. Treat., 2006, 98, 249-259.
66. Harris, J.C.; Cottrell, S.L.; Plummer, S.; Lloyd, D. Antimicrobialproperties of Allium sativum (garlic). Appl. Microbiol. Biotechnol.,2001, 57, 282-286.
67. Iciek, M.; Kwiecien, I.; Wlodek, L. Biological properties of garlicand garlicderived organosulfur compounds. Environ. Mol.Mutagen, 2009, 50, 247-265.
68. Standish, L.J.; Greene, K.B.; Bain, S.; Reeves, C.; Sanders, F.; Wines, R.C.; Turet, P.; Kim, J.G.; Calabrese, C. Alternative medicine use in HIV-positive men and women: demographics, utilization patterns and health status. AIDS Care, 2001, 13, 197-208.
69. Singh, U.P.; Prithiviraj, B.; Sarma, B.K.; Singh, M.; Ray, A.B. Role of garlic (Allium sativum L.) in human and plant diseases. In-dian J. Exp. Biol., 2001, 39, 310-322.
70. Foster, B.C.; Foster, M.S.; Vandenhoek, S.; Krantis, A.; Budzinski, J.W.; Arnason, J.T.; Gallicano, K.D.; Choudri, S. An in vitroevaluation of human cytochrome P450 3A4 and P-glycoprotein inhibition by garlic. J. Pharm. Pharm. Sci., 2001, 4, 176-184.
71. Piscitelli, S.C.; Burstein, A.H.; Welden, N.; Gallicano, K.D.; Falloon, J. The effect of garlic supplements on the pharmacokineticsof saquinavir. Clin. Infect. Dis., 2002, 34, 234-238.
72. Tanaka, S.; Haruma, K.; Yoshihara, M.; Kajiyama, G.; Kira, K.; Amagase, H.; Chayama, K. Aged garlic extract has potential sup-pressive effect on colorectal adenomas in humans. J. Nutr., 2006,136, 821S-826S.
73. Kelly, J.P.; Kaufman, D.W.; Kelley, K.; Rosenberg, L.; Anderson, T.E.; Mitchell, A.A. Recent trends in use of herbal and other natural products. Arch. Intern. Med., 2005, 165, 281-286.
74. van Beek, T.A. Chemical analysis of Ginkgo biloba leaves andextracts. J. Chromatogr. A, 2002, 967, 21-55.
75. Gurley, B.J.; Gardner, S.F.; Hubbard, M.A.; Williams, D.K.; Gentry, W.B.; Cui, Y.; Ang, C.Y. Cytochrome P450 phenotypic ratiosfor predicting herb-drug interactions in humans. Clin. Pharmacol.Ther., 2002, 72, 276-287.
76. Xu, A.H.; Chen, H.S.; Sun, B.C.; Xiang, X.R.; Chu, Y.F.; Zhai, F.; Jia, L.C. Therapeutic mechanism of ginkgo biloba exocarp poly-saccharides on gastric cancer. World J. Gastroenterol., 2003, 9,2424-2427.
77. Chen, H.S.; Zhai, F.; Chu, Y.F.; Xu, F.; Xu, A.H.; Jia, L.C. [Clinical study on treatment of patients with upper digestive tract malignant tumors of middle and late stage with Ginkgo biloba exocarppolysaccharides capsule preparation]. Zhong Xi Yi Jie He Xue Bao,2003, 1, 189-191.
78. Hauns, B.; Haring, B.; Kohler, S.; Mross, K.; Unger, C. Phase IIstudy of combined 5-fluorouracil/Ginkgo biloba extract (GBE 761ONC) therapy in 5-fluorouracil pretreated patients with advancedcolorectal cancer. Phytother. Res., 2001, 15, 34-38.
79. Hauns, B.; Haring, B.; Kohler, S.; Mross, K.; Robben-Bathe, P.; Unger, C. Phase II study with 5-fluorouracil and Ginkgo biloba ex-tract (GBE 761 ONC) in patients with pancreatic cancer. Arzneimit-telforschung, 1999, 49, 1030-1034.
80. Chang, Y.S.; Seo, E.K.; Gyllenhaal, C.; Block, K.I. Panax ginseng:a role in cancer therapy? Integr. Cancer Ther., 2003, 2, 13-33.
81. Jiang, X.; Williams, K.M.; Liauw, W.S.; Ammit, A.J.; Roufogalis, B.D.; Duke, C.C.; Day, R.O.; McLachlan, A.J. Effect of St John'swort and ginseng on the pharmacokinetics and pharmacodynamicsof warfarin in healthy subjects. Br. J. Clin. Pharmacol., 2004, 57,592-599.
82. Lee, S.H.; Ahn, Y.M.; Ahn, S.Y.; Doo, H.K.; Lee, B.C. Interactionbetween warfarin and Panax ginseng in ischemic stroke patients. J.Altern. Complement. Med., 2008, 14, 715-721.
83. Yuan, C.S.; Wei, G.; Dey, L.; Karrison, T.; Nahlik, L.; Maleckar, S.; Kasza, K.; Ang-Lee, M.; Moss, J. Brief communication: Ameri-can ginseng reduces warfarin's effect in healthy patients: a random-ized, controlled Trial. Ann. Intern. Med., 2004, 141, 23-27.
84. Shim, J.Y.; Han, Y.; Ahn, J.Y.; Yun, Y.S.; Song, J.Y. Chemoprotective and adjuvant effects of immunomodulator ginsan in cyclophosphamide-treated normal and tumor bearing mice. Int. J. Immunopathol. Pharmacol., 2007, 20, 487-497.
85. Block, K.I.; Mead, M.N. Immune system effects of echinacea,ginseng, and astragalus: a review. Integr. Cancer Ther., 2003, 2,247-267.
86. Shin, H.R.; Kim, J.Y.; Yun, T.K.; Morgan, G.; Vainio, H. Thecancer-preventive potential of Panax ginseng: a review of humanand experimental evidence. Cancer Causes Control, 2000, 11, 565-576.
87. Kim, J.H.; Park, C.Y.; Lee, S.J. Effects of sun ginseng on subjective quality of life in cancer patients: a double-blind, placebo-controlled pilot trial. J. Clin. Pharm. Ther., 2006, 31, 331-334.
88. Cui, Y.; Shu, X.O.; Gao, Y.T.; Cai, H.; Tao, M.H.; Zheng, W. Association of ginseng use with survival and quality of life amongbreast cancer patients. Am. J. Epidemiol., 2006, 163, 645-653.
89. Chrubasik, S.; Pittler, M.H.; Roufogalis, B.D. Zingiberis rhizoma: acomprehensive review on the ginger effect and efficacy profiles. Phytomedicine, 2005, 12, 684-701.
90. Boone, S.A.; Shields, K.M. Treating pregnancy-related nausea andvomiting with ginger. Ann. Pharmacother., 2005, 39, 1710-1713.
91. Ozgoli, G.; Goli, M.; Simbar, M. Effects of ginger capsules onpregnancy, nausea, and vomiting. J. Altern. Complement. Med.,2009, 15, 243-246.
92. Manusirivithaya, S.; Sripramote, M.; Tangjitgamol, S.; Sheanakul, C.; Leelahakorn, S.; Thavaramara, T.; Tangcharoenpanich, K. Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin. Int. J. Gynecol. Cancer, 2004, 14, 1063-1069.
93. Hickok, J.T.; Roscoe, J.A.; Morrow, G.R.; Ryan, J.L. A Phase II/IIIrandomized, placebo-controlled, double-blind clinical trial of gin-ger (Zingiber officinale) for nausea caused by chemotherapy forcancer: a currently accruing URCC CCOP cancer control study. Support. Cancer Ther., 2007, 4, 247-250.
94. Busby, L.T.; Jing, J.; Samlowski, W.E.; McGregor, J.R.; Farling, H.; Wheeler, R.H. Phase I and pharmacokinetic study of Kanglaiteinjection (KLT), a botanical product based on traditional ChineseMedicine. Proc. Am. Soc. Clin. Oncol. (ASCO) Ann. Meet., 2002,21.
95. Guo, H.Y.; Cai, Y.; Yang, X.M.; Wang, Z.H.; Wang, J.L.; Zhao, X.M.; Li, J.; Hu, X.C. Randomized Phase II trial on mitomycin-C/cisplatin ± KLT in heavily pretreated advanced breast cancer. Am. J. Chin. Med., 2008, 36, 665-674.
96. Gao, Y.H.; Zhou, S.F. Cancer prevention and treatment by Gano-derma, a mushroom with medicinal properties. Food Rev. Int.,2003, 19, 275-325.
97. Gao, Y.H.; Tang, W.B.; Gao, H.; Lan, J.; Zhou, S.F. Chemopreven-tive and tumoricidal properties of Ling Zhi mushroom Ganodermalucidum (W. Curt.:Fr.) Lioyd (Aphyllophoromycetideae). Part I.Preclinical studies. Int. J. Med. Mushr., 2004, 6, 95-106.
98. Gao, Y.H.; Tang, W.B.; Gao, H.; Lan, J.; Zhou, S.F. Chemopreventive and tumoricidal properties of Ling Zhi mushroom Ganodermalucidum (W. Curt.:Fr.) Lioyd (Aphyllophoromycetideae). Part II.Mechanism considerations. Int. J. Med. Mushr., 2004, 6, 219-230.
99. Gao, Y.H.; Zhou, S.F.; Jiang, W.Q.; Huang, M.; X.H., D. Effect ofGanopoly, a Ganoderma lucidum polysaccharide extract on theimmunological function in advanced-stage cancer patients. Immunol. Invest., 2003, 32, 201-215.
100. Wachtel-Galor, S.; Tomlinson, B.; Benzie, I.F. Ganoderma lucidum (Lingzhi), a Chinese medicinal mushroom: biomarker responses in a controlled human supplementation study. Br. J. Nutr.,2004, 91, 263-269.
101. Gao, Y.H.; Chen, G.L.; Dai, X.H.; Ye, J.X.; Zhou, S.F. A Phase I/IIstudy of a Ganoderma lucidum extract (Ganopoly) in patients withadvanced cancer. Int. J. Med. Mushr., 2002, 4, 207-214.
102. Gao, Y.H.; Dai, X.H.; Chen, G.L.; Ye, J.X.; Zhou, S.F. A radomized, placebo-controlled, multicenter study of Ganoderma lucidum(W.Curt.:Fr.)Lloyd (Aphyllophoromycetideae) polysaccharides(Ganopoly) in patients with advanced lung cancer. Int. J. Med.Mushr., 2003, 5, 383-395.
103. Kroll, D.J.; Shaw, H.S.; Oberlies, N.H. Milk thistle nomenclature:why it matters in cancer research and pharmacokinetic studies. Integr. Cancer Ther., 2007, 6, 110-119.
104. Pradhan, S.C.; Girish, C. Hepatoprotective herbal drug, silymarinfrom experimental pharmacology to clinical medicine. Indian J.Med. Res., 2006, 124, 491-504.
105. Das, S.K.; Vasudevan, D.M. Protective effects of silymarin, a milkthistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver. Indian J. Biochem. Biophys., 2006, 43, 306-311.
106. Comelli, M.C.; Mengs, U.; Schneider, C.; Prosdocimi, M. Towardthe definition of the mechanism of action of silymarin: activities related to cellular protection from toxic damage induced by chemotherapy. Integr. Cancer Ther., 2007, 6, 120-129.
107. Sagar, S.M. Future directions for research on Silybum marianumfor cancer patients. Integr. Cancer Ther., 2007, 6, 166-173.
108. Tamayo, C.; Diamond, S. Review of clinical trials evaluating safetyand efficacy of milk thistle (Silybum marianum [L.] Gaertn.). Integr. Cancer Ther., 2007, 6, 146-157.
109. Wallace, S.; Carrier, D.; Clausen, E. Extraction of nutraceuticalsfrom milk thistle: Part II. Extraction with organic solvents. Appl.Biochem. Biotechnol., 2003, 108, 891-904.
110. Kvasnicka, F.; Biba, B.; Sevcik, R.; Voldrich, M.; Kratka, J. Analysis of the active components of silymarin. J. Chromatogr. A,2003, 990, 239-245.
111. Mansour, H.H.; Hafez, H.F.; Fahmy, N.M. Silymarin modulatescisplatin-induced oxidative stress and hepatotoxicity in rats. J. Biochem. Mol. Biol., 2006, 39, 656-661.
112. Gaedeke, J.; Fels, L.M.; Bokemeyer, C.; Mengs, U.; Stolte, H.; Lentzen, H. Cisplatin nephrotoxicity and protection by silibinin. Nephrol. Dial. Transplant., 1996, 11, 55-62.
113. Karimi, G.; Ramezani, M.; Tahoonian, Z. Cisplatin nephrotoxicityand protection by milk thistle extract in rats. Evid. Based Complement. Alternat. Med., 2005, 2, 383-386.
114. Singh, R.P.; Raina, K.; Deep, G.; Chan, D.; Agarwal, R. Silibininsuppresses growth of human prostate carcinoma PC-3 orthotopicxenograft via activation of extracellular signal-regulated kinase 1/2and inhibition of signal transducers and activators of transcriptionsignaling. Clin. Cancer Res., 2009, 15, 613-621.
115. Singh, R.P.; Raina, K.; Sharma, G.; Agarwal, R. Silibinin inhibitsestablished prostate tumor growth, progression, invasion, and me-tastasis and suppresses tumor angiogenesis and epithelial-mesenchymal transition in transgenic adenocarcinoma of the mouseprostate model mice. Clin. Cancer Res., 2008, 14, 7773-7780.
116. Singh, R.P.; Tyagi, A.; Sharma, G.; Mohan, S.; Agarwal, R. Oralsilibinin inhibits in vivo human bladder tumor xenograft growth in-volving down-regulation of survivin. Clin. Cancer Res., 2008, 14,300-308.
117. Raina, K.; Rajamanickam, S.; Singh, R.P.; Deep, G.; Chittezhath, M.; Agarwal, R. Stage-specific inhibitory effects and associatedmechanisms of silibinin on tumor progression and metastasis intransgenic adenocarcinoma of the mouse prostate model. Cancer Res., 2008, 68, 6822-6830.
118. Gallo, D.; Giacomelli, S.; Ferlini, C.; Raspaglio, G.; Apollonio, P.; Prislei, S.; Riva, A.; Morazzoni, P.; Bombardelli, E.; Scambia, G. Antitumour activity of the silybin-phosphatidylcholine complex,IdB 1016, against human ovarian cancer. Eur. J. Cancer, 2003, 39,2403-2410.
119. Flaig, T.W.; Gustafson, D.L.; Su, L.J.; Zirrolli, J.A.; Crighton, F.; Harrison, G.S.; Pierson, A.S.; Agarwal, R.; Glode, L.M. A Phase Iand pharmacokinetic study of silybin-phytosome in prostate cancerpatients. Invest. New Drugs, 2007, 25, 139-146.
120. Kidd, P.; Head, K. A review of the bioavailability and clinicalefficacy of milk thistle phytosome: a silybin-phosphatidylcholinecomplex (Siliphos). Altern. Med. Rev., 2005, 10, 193-203.
121. Hoh, C.; Boocock, D.; Marczylo, T.; Singh, R.; Berry, D.P.; Dennison, A.R.; Hemingway, D.; Miller, A.; West, K.; Euden, S.; Garcea, G.; Farmer, P.B.; Steward, W.P.; Gescher, A.J. Pilot study oforal silibinin, a putative chemopreventive agent, in colorectal cancer patients: silibinin levels in plasma, colorectum, and liver andtheir pharmacodynamic consequences. Clin. Cancer Res., 2006, 12,2944-2950.
122. Schroder, F. H.; Roobol, M. J.; Boeve, E. R.; de Mutsert, R.; Zui-jdgeest-van Leeuwen, S. D.; Kersten, I.; Wildhagen, M. F.; van Helvoort, A. Randomized, double-blind, placebo-controlled crossoverstudy in men with prostate cancer and rising PSA: effectiveness ofa dietary supplement. Eur. Urol., 2005, 48, 922-930; discussion930-921.
123. Kim, Y.C.; Kim, E.J.; Lee, E.D.; Kim, J.H.; Jang, S.W.; Kim, Y.G.; Kwon, J.W.; Kim, W.B.; Lee, M.G. Comparative bioavailability ofsilibinin in healthy male volunteers. Int. J. Clin. Pharmacol. Ther.,2003, 41, 593-596.
124. Wen, Z.; Dumas, T.E.; Schrieber, S.J.; Hawke, R.L.; Fried, M.W.; Smith, P.C. Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma afteroral administration of milk thistle extract. Drug Metab. Dispos.,2008, 36, 65-72.
125. Wu, J.W.; Lin, L.C.; Tsai, T.H. Drug-drug interactions of silymarinon the perspective of pharmacokinetics. J. Ethnopharmacol., 2009,121, 185-193.
126. Schrieber, S.J.; Wen, Z.; Vourvahis, M.; Smith, P.C.; Fried, M.W.; Kashuba, A.D.; Hawke, R.L. The pharmacokinetics of silymarin isaltered in patients with hepatitis C virus and nonalcoholic fattyliver disease and correlates with plasma caspase-3/7 activity. DrugMetab. Dispos., 2008, 36, 1909-1916.
127. Kren, V.; Ulrichova, J.; Kosina, P.; Stevenson, D.; Sedmera, P.; Prikrylova, V.; Halada, P.; Simanek, V. Chemoenzymatic preparation of silybin-glucuronides and their biological evaluation. Drug Metab. Dispos., 2000, 28, 1513-1517.
128. Jancova, P.; Anzenbacherova, E.; Papouskova, B.; Lemr, K.; Luzna, P.; Veinlichova, A.; Anzenbacher, P.; Simanek, V. Silybinis metabolized by cytochrome P450 2C8 in vitro. Drug Metab.Dispos., 2007, 35, 2035-2039.
129. Beckmann-Knopp, S.; Rietbrock, S.; Weyhenmeyer, R.; Bocker, R.H.; Beckurts, K.T.; Lang, W.; Hunz, M.; Fuhr, U. Inhibitory ef-fects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol. Toxicol., 2000, 86, 250-256.
130. Sridar, C.; Goosen, T.C.; Kent, U.M.; Williams, J.A.; Hollenberg, P.F. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab. Dispos.,2004, 32, 587-594.
131. Mazzio, E.A.; Soliman, K.F. In vitro screening for the tumoricidalproperties of international medicinal herbs. Phytother. Res., 2009,23, 385-398.
132. Zarkovic, N.; Vukovic, T.; Loncaric, I.; Miletic, M.; Zarkovic, K.; Borovic, S.; Cipak, A.; Sabolovic, S.; Konitzer, M.; Mang, S. Anoverview on anticancer activities of the Viscum album extractIsorel. Cancer Biother. Radiopharm., 2001, 16, 55-62.
133. Thies, A.; Dautel, P.; Meyer, A.; Pfuller, U.; Schumacher, U. Low-dose mistletoe lectin-I reduces melanoma growth and spread in ascid mouse xenograft model. Br. J. Cancer, 2008, 98, 106-112.
134. Kelter, G.; Schierholz, J.M.; Fischer, I.U.; Fiebig, H.H. Cytotoxicactivity and absence of tumor growth stimulation of standardizedmistletoe extracts in human tumor models in vitro. Anticancer Res.,2007, 27, 223-233.
135. Grossarth-Maticek, R.; Ziegler, R. Prospective controlled cohortstudies on long-term therapy of ovairian cancer patients with mistletoe (Viscum album L.) extracts iscador. Arzneimittelforschung,2007, 57, 665-678.
136. Grossarth-Maticek, R.; Ziegler, R. Prospective controlled cohortstudies on long-term therapy of cervical cancer patients with a mistletoe preparation (Iscador). Forsch Komplementmed., 2007, 14,140-147.
137. Kirsch, A. Successful treatment of metastatic malignant melanomawith Viscum album extract (Iscador M). J. Altern. Complement.Med., 2007, 13, 443-445.
138. Ziegler, R.; Grossarth-Maticek, R. Individual patient data meta-analysis of survival and psychosomatic self-regulation from published prospective controlled cohort studies for long-term therapyof breast cancer patients with a mistletoe preparation (Iscador). Evid. Based Complement. Alternat. Med., 2009 (Epub ahead ofprint).
139. Kienle, G.S.; Glockmann, A.; Schink, M.; Kiene, H. Viscum albumL. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research. J. Exp. Clin. Cancer Res.,2009, 28, 79.
140. Gardin, N.E. Immunological response to mistletoe (Viscum albumL.) in cancer patients: a four-case series. Phytother. Res., 2009, 23,407-411.
141. Kleijnen, J.; Knipschild, P. Mistletoe treatment for cancer: Reviewof controlled trials in humans. Phytomedicine, 1994, 1, 255-260.
142. Ernst, E.; Schmidt, K.; Steuer-Vogt, M.K. Mistletoe for cancer? Asystematic review of randomised clinical trials. Int. J. Cancer,2003, 107, 262-267.
143. Kienle, G.S.; Berrino, F.; Bussing, A.; Portalupi, E.; Rosenzweig, S.; Kiene, H. Mistletoe in cancer-a systematic review on controlled clinical trials. Eur. J. Med. Res., 2003, 8, 109-119.
144. Grossarth-Maticek, R.; Kiene, H.; Baumgartner, S. M.; Ziegler, R. Use of Iscador, an extract of European mistletoe (Viscum album),in cancer treatment: prospective nonrandomized and randomizedmatched-pair studies nested within a cohort study. Altern. Ther. Health Med., 2001, 7, 57-66, 68-72, 74-56 passim.
145. Steuer-Vogt, M.K.; Bonkowsky, V.; Ambrosch, P.; Scholz, M.; Neiss, A.; Strutz, J.; Hennig, M.; Lenarz, T.; Arnold, W. The effectof an adjuvant mistletoe treatment programme in resected head andneck cancer patients: a randomised controlled clinical trial. Eur. J.Cancer, 2001, 37, 23-31.
146. Schumacher, K.; Schneider, B.; Reich, G.; Stiefel, T.; Stoll, G.; Bock, P.R.; Hanisch, J.; Beuth, J. Influence of postoperative complementary treatment with lectin-standardized mistletoe extract onbreast cancer patients. A controlled epidemiological multicentricretrolective cohort study. Anticancer Res., 2003, 23, 5081-5087.
147. Kienle, G.S.; Kiene, H. Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts. Eur. J. Med. Res., 2007, 12, 103-119.
148. Horneber, M. A.; Bueschel, G.; Huber, R.; Linde, K.; Rostock, M. Mistletoe therapy in oncology. Cochrane Database Syst. Rev.,2008, CD003297.
149. Kase, Y.; Saitoh, K.; Makino, B.; Hashimoto, K.; Ishige, A.; Komatsu, Y. Relationship between the antidiarrhoeal effects of Hange-Shashin-To and its active components. Phytother. Res.,1999, 13, 468-473.
150. Mori, K.; Kondo, T.; Kamiyama, Y.; Kano, Y.; Tominaga, K. Preventive effect of Kampo medicine (Hangeshashin-to) against iri-notecan-induced diarrhea in advanced non-small-cell lung cancer.Cancer Chemother. Pharmacol., 2003, 51, 403-406.
151. Kase, Y.; Hayakawa, T.; Aburada, M.; Komatsu, Y.; Kamataki, T. Preventive effects of Hange-shashin-to on irinotecan hydrochlo-ride-caused diarrhea and its relevance to the colonic prostaglandinE2 and water absorption in the rat. Jpn. J. Pharmacol., 1997, 75,407-413.
152. Narita, M.; Nagai, E.; Hagiwara, H.; Aburada, M.; Yokoi, T.; Kamataki, T. Inhibition of-glucuronidase by natural glucuronides ofkampo medicines using glucuronide of SN-38 (7-ethyl-10-hydroxycamptothecin) as a substrate. Xenobiotica, 1993, 23, 5-10.
153. Satoh, H.; Ishikawa, H.; Ohtsuka, M.; Sekizawa, K. Japaneseherbal medicine in patients with advanced lung cancer: prolongation of survival. J. Altern. Complement. Med., 2002, 8, 107-108.
154. Amato, P.; Christophe, S.; Mellon, P.L. Estrogenic activity of herbscommonly used as remedies for menopausal symptoms. Meno-pause, 2002, 9, 145-150.
155. Kudoh, S.; Fujiwara, Y.; Takada, Y.; Yamamoto, H.; Kinoshita, A.; Ariyoshi, Y.; Furuse, K.; Fukuoka, M. Phase II study of irinotecancombined with cisplatin in patients with previously untreatedsmall-cell lung cancer. West Japan Lung Cancer Group. J. Clin.Oncol., 1998, 16, 1068-1074.
156. Humerickhouse, R.; Lohrbach, K.; Li, L.; Bosron, W.F.; Dolan, M.E. Characterization of CPT-11 hydrolysis by human liver car-boxylesterase isoforms hCE-1 and hCE-2. Cancer Res., 2000, 60,1189-1192.
157. Bencharit, S.; Morton, C.L.; Howard-Williams, E.L.; Danks, M.K.; Potter, P.M.; Redinbo, M.R. Structural insights into CPT-11 activation by mammalian carboxylesterases. Nat. Struct. Biol., 2002, 9,337-342.
158. Hanioka, N.; Ozawa, S.; Jinno, H.; Ando, M.; Saito, Y.; Sawada, J. Human liver UDP-glucuronosyltransferase isoforms involved in theglucuronidation of 7-ethyl-10-hydroxycamptothecin. Xenobiotica,2001, 31, 687-699.
159. Mathijssen, R.H.J.; van Alphen, R.J.; Verweij, J.; Loos, W.J.; Nooter, K.; Stoter, G.; Sparreboom, A. Clinical pharmacokineticsand metabolism of irinotecan (CPT-11). Clin. Cancer Res., 2001, 7,2182-2194.
160. Chu, X.Y.; Kato, Y.; Niinuma, K.; Sudo, K.I.; Hakusui, H.; Sugiyama, Y. Multispecific organic anion transporter is responsible forthe biliary excretion of the camptothecin derivative irinotecan andits metabolites in rats. J. Pharmacol. Exp. Ther., 1997, 281, 304-314.
161. Santos, A.; Zanetta, S.; Cresteil, T.; Deroussent, A.; Pein, F.; Raymond, E.; Vernillet, L.; Risse, M.L.; Boige, V.; Gouyette, A.; Vassal, G. Metabolism of irinotecan (CPT-11) by CYP3A4 andCYP3A5 in humans. Clin. Cancer Res., 2000, 6, 2012-2020.
162. Kehrer, D.F.; Yamamoto, W.; Verweij, J.; de Jonge, M.J.; deBruijn, P.; Sparreboom, A. Factors involved in prolongation of theterminal disposition phase of SN-38: clinical and experimentalstudies. Clin. Cancer Res., 2000, 6, 3451-3458.
163. Rothenberg, M.L. Irinotecan (CPT-11): recent developments andfuture directions-colorectal cancer and beyond. Oncologist, 2001,6, 66-80.
164. Sugiyama, Y.; Kato, Y.; Chu, X. Multiplicity of biliary excretionmechanisms for the camptothecin derivative irinotecan (CPT-11),its metabolite SN-38, and its glucuronide: role of canalicular mul-tispecific organic anion transporter and P-glycoprotein. Cancer Chemother. Pharmacol., 1998, 42(Suppl), S44-49.
165. Chu, X.Y.; Suzuki, H.; Ueda, K.; Kato, Y.; Akiyama, S.; Sugi-yama, Y. Active efflux of CPT-11 and its metabolites in humanKB-derived cell lines. J. Pharmacol. Exp. Ther., 1999, 288, 735-741.
166. Maliepaard, M.; van Gastelen, M.A.; Tohgo, A.; Hausheer, F.H.; van Waardenburg, R.C.; de Jong, L.A.; Pluim, D.; Beijnen, J.H.; Schellens, J.H. Circumvention of breast cancer resistance protein(BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin. CancerRes., 2001, 7, 935-941.
167. Mathijssen, R.H.; Verweij, J.; de Bruijn, P.; Loos, W.J.; Sparre-boom, A. Effects of St. John's wort on irinotecan metabolism. J.Natl. Cancer Inst., 2002, 94, 1247-1249.
168. Hu, Z.P.; Yang, X.X.; Chen, X.; Cao, J.; Chan, E.; Duan, W.; Huang, M.; Yu, X.Q.; Wen, J.Y.; Zhou, S.F. A mechanistic studyon altered pharmacokinetics of irinotecan by St. John's wort. Curr.Drug Metab., 2007, 8, 157-171.
169. Hu, Z.; Yang, X.; Ho, P.C.; Chan, E.; Chan, S.Y.; Xu, C.; Li, X.; Zhu, Y.Z.; Duan, W.; Chen, X.; Huang, M.; Yang, H.; Zhou, S. St. John's wort modulates the toxicities and pharmacokinetics of CPT-11 (irinotecan) in rats. Pharm. Res., 2005, 22, 902-914.
170. Hu, Z.P.; Yang, X.X.; Chan, S.Y.; Xu, A.L.; Duan, W.; Zhu, Y.Z.; Sheu, F.S.; Boelsterli, U.A.; Chan, E.; Zhang, Q.; Wang, J.C.; Ee, P.L.; Koh, H.L.; Huang, M.; Zhou, S.F. St. John's wort attenuatesirinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis. Toxicol. Appl. Pharmacol., 2006, 216, 225-237.
171. Linde, K.; Mulrow, C. D.; Berner, M.; Egger, M. St John's wort fordepression. Cochrane Database Syst. Rev., 2005, CD000448.
172. Moore, L.B.; Goodwin, B.; Jones, S.A.; Wisely, G.B.; Serabjit-Singh, C.J.; Willson, T.M.; Collins, J.L.; Kliewer, S.A. St. John'swort induces hepatic drug metabolism through activation of thepregnane X receptor. Proc. Natl. Acad. Sci. U. S. A., 2000, 97,7500-7502.
173. Goodwin, B.; Moore, L.B.; Stoltz, C.M.; McKee, D.D.; Kliewer, S.A. Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor. Mol. Pharmacol., 2001, 60, 427-431.
174. Obach, R.S. Inhibition of human cytochrome P450 enzymes byconstituents of St. John's wort, an herbal preparation used in thetreatment of depression. J. Pharmacol. Exp. Ther., 2000, 294, 88-95.
175. Roby, C.A.; Anderson, G.D.; Kantor, E.; Dryer, D.A.; Burstein, A.H. St John's wort: effect on CYP3A4 activity. Clin. Pharmacol. Ther., 2000, 67, 451-457.
176. Wang, Z.Q.; Gorski, C.; Hamman, M.A.; Huang, S.M.; Lesko, L.J.; Hall, S.D. The effects of St John's wort (Hypericum perforatum) onhuman cytochrome P450 activity. Clin. Pharmacol. Ther., 2001,70, 317-326.
177. Han, Y.; Guo, D.; Chen, Y.; Chen, Y.; Tan, Z.R.; Zhou, H.H. Ef-fect of silymarin on the pharmacokinetics of losartan and its activemetabolite E-3174 in healthy Chinese volunteers. Eur. J. Clin.Pharmacol., 2009, 65, 585-591.
178. Rajnarayana, K.; Reddy, M.S.; Vidyasagar, J.; Krishna, D.R. Studyon the influence of silymarin pretreatment on metabolism and dis-position of metronidazole. Arzneimittelforschung, 2004, 54, 109-113.
179. Fuhr, U.; Beckmann-Knopp, S.; Jetter, A.; Luck, H.; Mengs, U. The effect of silymarin on oral nifedipine pharmacokinetics. PlantaMed., 2007, 73, 1429-1435.
180. Gurley, B.J.; Barone, G.W.; Williams, D.K.; Carrier, J.; Breen, P.; Yates, C.R.; Song, P.F.; Hubbard, M.A.; Tong, Y.; Cheboyina, S. Effect of milk thistle (Silybum marianum) and black cohosh (Cimi-cifuga racemosa) supplementation on digoxin pharmacokinetics inhumans. Drug Metab. Dispos., 2006, 34, 69-74.
181. Mills, E.; Wilson, K.; Clarke, M.; Foster, B.; Walker, S.; Rachlis, B.; DeGroot, N.; Montori, V.M.; Gold, W.; Phillips, E.; Myers, S.; Gallicano, K. Milk thistle and indinavir: a randomized controlledpharmacokinetics study and meta-analysis. Eur. J. Clin. Pharma-col., 2005, 61, 1-7.
182. Deng, J.W.; Shon, J.H.; Shin, H.J.; Park, S.J.; Yeo, C.W.; Zhou, H.H.; Song, I.S.; Shin, J.G. Effect of silymarin supplement on thepharmacokinetics of rosuvastatin. Pharm. Res., 2008, 25, 1807-1814.
183. Gurley, B.J.; Swain, A.; Hubbard, M.A.; Williams, D.K.; Barone, G.; Hartsfield, F.; Tong, Y.; Carrier, D.J.; Cheboyina, S.; Battu, S.K. Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal,kava kava, St. John's wort, and Echinacea. Mol. Nutr. Food Res.,2008, 52, 755-763.
184. Rao, B.N.; Srinivas, M.; Kumar, Y.S.; Rao, Y.M. Effect of silymarin on the oral bioavailability of ranitidine in healthy humanvolunteers. Drug Metabol. Drug Interact., 2007, 22, 175-185.
185. Gurley, B.; Hubbard, M.A.; Williams, D.K.; Thaden, J.; Tong, Y.; entry, W.B.; Breen, P.; Carrier, D.J.; Cheboyina, S. Assessing theclinical significance of botanical supplementation on human cyto-chrome P450 3A activity: comparison of a milk thistle and blackcohosh product to rifampin and clarithromycin. J. Clin. Pharma-col., 2006, 46, 201-213.
186. Gurley, B.J.; Gardner, S.F.; Hubbard, M.A.; Williams, D.K.; Gen-try, W.B.; Carrier, J.; Khan, I.A.; Edwards, D.J.; Shah, A. In vivoassessment of botanical supplementation on human cytochromeP450 phenotypes: Citrus aurantium, Echinacea purpurea, milkthistle, and saw palmetto. Clin. Pharmacol. Ther., 2004, 76, 428-440.
187. van Erp, N.P.; Baker, S.D.; Zhao, M.; Rudek, M.A.; Guchelaar, H.J.; Nortier, J.W.; Sparreboom, A.; Gelderblom, H. Effect of milkthistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin. Cancer Res., 2005, 11, 7800-7806.
188. Zhang, S.; Morris, M.E. Effects of the flavonoids biochanin A,morin, phloretin, and silymarin on P-glycoprotein-mediated trans-port. J. Pharmacol. Exp. Ther., 2003, 304, 1258-1267.
189. Johnson, J.R.; Bross, P.; Cohen, M.; Rothmann, M.; Chen, G.; Zajicek, A.; Gobburu, J.; Rahman, A.; Staten, A.; Pazdur, R. Approval summary: imatinib mesylate capsules for treatment of adultpatients with newly diagnosed philadelphia chromosome-positivechronic myelogenous leukemia in chronic phase. Clin. Cancer Res.,2003, 9, 1972-1979.
190. Cohen, M.H.; Johnson, J.R.; Pazdur, R. U.S. Food and Drug Administration Drug Approval Summary: conversion of imatinib me-sylate (STI571; Gleevec) tablets from accelerated approval to fullapproval. Clin. Cancer Res., 2005, 11, 12-19.
191. Gschwind, H.P.; Pfaar, U.; Waldmeier, F.; Zollinger, M.; Sayer, C.; Zbinden, P.; Hayes, M.; Pokorny, R.; Seiberling, M.; Ben-Am, M.; Peng, B.; Gross, G. Metabolism and disposition of imatinib mesy-late in healthy volunteers. Drug Metab. Dispos., 2005, 33, 1503-1512.
192. van Erp, N.P.; Gelderblom, H.; Karlsson, M.O.; Li, J.; Zhao, M.; Ouwerkerk, J.; Nortier, J.W.; Guchelaar, H.J.; Baker, S.D.; Sparreboom, A. Influence of CYP3A4 inhibition on the steady-statepharmacokinetics of imatinib. Clin. Cancer Res., 2007, 13, 7394-7400.
193. Ma, S.; Xu, Y.; Shou, M. Characterization of imatinib metabolitesin rat and human liver microsomes: differentiation of hydroxylationfrom N-oxidation by liquid chromatography/atmospheric pressurechemical ionization mass spectrometry. Rapid Commun. Mass Spectrom., 2009, 23, 1446-1450.
194. Ma, S.; Subramanian, R.; Xu, Y.; Schrag, M.; Shou, M. Structuralcharacterization of novel adenine dinucleotide phosphate conju-gates of imatinib in incubations with rat and human liver micro-somes. Drug Metab. Dispos., 2008, 36, 2414-2418.
195. Gardner, E.R.; Burger, H.; van Schaik, R.H.; van Oosterom, A.T.; de Bruijn, E.A.; Guetens, G.; Prenen, H.; de Jong, F.A.; Baker, S.D.; Bates, S.E.; Figg, W.D.; Verweij, J.; Sparreboom, A.; Nooter, K. Association of enzyme and transporter genotypes with thepharmacokinetics of imatinib. Clin. Pharmacol. Ther., 2006, 80,192-201.
196. Dutreix, C.; Peng, B.; Mehring, G.; Hayes, M.; Capdeville, R.; Pokorny, R.; Seiberling, M. Pharmacokinetic interaction betweenketoconazole and imatinib mesylate (Glivec) in healthy subjects.Cancer Chemother. Pharmacol., 2004, 54, 290-294.
197. O'Brien, S.G.; Meinhardt, P.; Bond, E.; Beck, J.; Peng, B.; Dutreix, C.; Mehring, G.; Milosavljev, S.; Huber, C.; Capdeville, R.; Fischer, T. Effects of imatinib mesylate (STI571, Glivec) on thepharmacokinetics of simvastatin, a cytochrome P450 3A4 sub-strate, in patients with chronic myeloid leukaemia. Br. J. Cancer,2003, 89, 1855-1859.
198. Wang, Y.; Zhou, L.; Dutreix, C.; Leroy, E.; Yin, Q.; Sethuraman, V.; Riviere, G.J.; Yin, O.Q.; Schran, H.; Shen, Z.X. Effects ofimatinib (Glivec) on the pharmacokinetics of metoprolol, aCYP2D6 substrate, in Chinese patients with chronic myelogenousleukaemia. Br. J. Clin. Pharmacol., 2008, 65, 885-892.
199. Frye, R.F.; Fitzgerald, S.M.; Lagattuta, T.F.; Hruska, M.W.; Egorin, M.J. Effect of St John's wort on imatinib mesylate pharma-cokinetics. Clin. Pharmacol. Ther., 2004, 76, 323-329.
200. Smith, P.; Bullock, J.M.; Booker, B.M.; Haas, C.E.; Berenson, C.S.; Jusko, W.J. The influence of St. John's wort on the pharma-cokinetics and protein binding of imatinib mesylate. Pharma-cotherapy, 2004, 24, 1508-1514.
201. Bolton, A.E.; Peng, B.; Hubert, M.; Krebs-Brown, A.; Capdeville, R.; Keller, U.; Seiberling, M. Effect of rifampicin on the pharma-cokinetics of imatinib mesylate (Gleevec, STI571) in healthy sub-jects. Cancer Chemother. Pharmacol., 2004, 53, 102-106.
202. Bauer, S.; Stormer, E.; Johne, A.; Kruger, H.; Budde, K.; Neu-mayer, H.H.; Roots, I.; Mai, I. Alterations in cyclosporin A phar-macokinetics and metabolism during treatment with St John's wortin renal transplant patients. Br. J. Clin. Pharmacol., 2003, 55, 203-211.
203. Mai, I.; Stormer, E.; Bauer, S.; Kruger, H.; Budde, K.; Roots, I.Impact of St John's wort treatment on the pharmacokinetics of tac-rolimus and mycophenolic acid in renal transplant patients. Neph-rol. Dial. Transplant., 2003, 18, 819-822.
204. Hamada, A.; Miyano, H.; Watanabe, H.; Saito, H. Interaction ofimatinib mesilate with human P-glycoprotein. J. Pharmacol. Exp.Ther., 2003, 307, 824-828.
205. Ozvegy-Laczka, C.; Hegedus, T.; Varady, G.; Ujhelly, O.; Schuetz, J.D.; Varadi, A.; Keri, G.; Orfi, L.; Nemet, K.; Sarkadi, B. High-affinity interaction of tyrosine kinase inhibitors with the ABCG2multidrug transporter. Mol. Pharmacol., 2004, 65, 1485-1495.
206. Hu, S.; Franke, R.M.; Filipski, K.K.; Hu, C.; Orwick, S.J.; deBruijn, E.A.; Burger, H.; Baker, S.D.; Sparreboom, A. Interactionof imatinib with human organic ion carriers. Clin. Cancer Res.,2008, 14, 3141-3148.
207. Oostendorp, R.L.; Buckle, T.; Beijnen, J.H.; van Tellingen, O.; Schellens, J.H. The effect of P-gp (Mdr1a/1b), BCRP (Bcrp1) andP-gp/BCRP inhibitors on the in vivo absorption, distribution, me-tabolism and excretion of imatinib. Invest. New Drugs, 2009, 27,31-40.
208. Dowell, J.; Minna, J.D.; Kirkpatrick, P. Erlotinib hydrochloride. Nat. Rev. Drug Discov., 2005, 4, 13-14.
209. Johnson, J.R.; Cohen, M.; Sridhara, R.; Chen, Y.F.; Williams, G.M.; Duan, J.; Gobburu, J.; Booth, B.; Benson, K.; Leighton, J.; Hsieh, L.S.; Chidambaram, N.; Zimmerman, P.; Pazdur, R. Ap-proval summary for erlotinib for treatment of patients with locallyadvanced or metastatic non-small cell lung cancer after failure of atleast one prior chemotherapy regimen. Clin. Cancer Res., 2005, 11,6414-6421.
210. Moore, M.J.; Goldstein, D.; Hamm, J.; Figer, A.; Hecht, J.R.; Gall-inger, S.; Au, H.J.; Murawa, P.; Walde, D.; Wolff, R.A.; Campos, D.; Lim, R.; Ding, K.; Clark, G.; Voskoglou-Nomikos, T.; Ptasyn-ski, M.; Parulekar, W. Erlotinib plus gemcitabine compared withgemcitabine alone in patients with advanced pancreatic cancer: aPhase III trial of the National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol., 2007, 25, 1960-1966.
211. Van Cutsem, E.; Vervenne, W.L.; Bennouna, J.; Humblet, Y.; Gill, S.; Van Laethem, J.L.; Verslype, C.; Scheithauer, W.; Shang, A.; Cosaert, J.; Moore, M.J. Phase III trial of bevacizumab in combina-tion with gemcitabine and erlotinib in patients with metastatic pan-creatic cancer. J. Clin. Oncol., 2009, 27, 2231-2237.
212. Saif, M.W. Erlotinib: the first biologic in the management of pan-creatic cancer. Expert Opin. Pharmacother., 2008, 9, 1595-1607.
213. Gridelli, C.; Butts, C.; Ciardiello, F.; Feld, R.; Gallo, C.; Perrone, F. An international, multicenter, randomized Phase III study offirst-line erlotinib followed by second-line cisplatin/gemcitabineversus first-line cisplatin/gemcitabine followed by second-line er-lotinib in advanced non-small-cell lung cancer: treatment rationaleand protocol dynamics of the TORCH trial. Clin. Lung Cancer,2008, 9, 235-238.
214. Gridelli, C.; Bareschino, M.A.; Schettino, C.; Rossi, A.; Maione, P.; Ciardiello, F. Erlotinib in non-small cell lung cancer treatment:current status and future development. Oncologist, 2007, 12, 840-849.
215. Frohna, P.; Lu, J.; Eppler, S.; Hamilton, M.; Wolf, J.; Rakhit, A.; Ling, J.; Kenkare-Mitra, S.R.; Lum, B.L. Evaluation of the absoluteoral bioavailability and bioequivalence of erlotinib, an inhibitor ofthe epidermal growth factor receptor tyrosine kinase, in a random-ized, crossover study in healthy subjects. J. Clin. Pharmacol.,2006, 46, 282-290.
216. Ling, J.; Johnson, K.A.; Miao, Z.; Rakhit, A.; Pantze, M.P.; Hamilton, M.; Lum, B.L.; Prakash, C. Metabolism and excretion of erlotinib, a small molecule inhibitor of epidermal growth factor receptor tyrosine kinase, in healthy male volunteers. Drug Metab. Dispos., 2006, 34, 420-426.
217. Li, J.; Zhao, M.; He, P.; Hidalgo, M.; Baker, S.D. Differentialmetabolism of gefitinib and erlotinib by human cytochrome P450enzymes. Clin. Cancer Res., 2007, 13, 3731-3737.
218. Rakhit, A.; Pantze, M.P.; Fettner, S.; Jones, H.M.; Charoin, J.E.; Riek, M.; Lum, B.L.; Hamilton, M. The effects of CYP3A4 inhibi-tion on erlotinib pharmacokinetics: computer-based simulation(SimCYP) predicts in vivo metabolic inhibition. Eur. J. Clin. Pharmacol., 2008, 64, 31-41.
219. Granfors, M.T.; Backman, J.T.; Neuvonen, M.; Neuvonen, P.J. Ciprofloxacin greatly increases concentrations and hypotensive ef-fect of tizanidine by inhibiting its cytochrome P450 1A2-mediatedpresystemic metabolism. Clin. Pharmacol. Ther., 2004, 76, 598-606.
220. Cohen, M.H.; Johnson, J.R.; Chen, Y.F.; Sridhara, R.; Pazdur, R. FDA drug approval summary: erlotinib (Tarceva) tablets. Oncologist, 2005, 10, 461-466.
221. Grenader, T.; Gipps, M.; Shavit, L.; Gabizon, A. Significant druginteraction: phenytoin toxicity due to erlotinib. Lung Cancer, 2007,57, 404-406.
222. Harmsen, S.; Meijerman, I.; Beijnen, J.H.; Schellens, J.H. Nuclearreceptor mediated induction of cytochrome P450 3A4 by anticancerdrugs: a key role for the pregnane X receptor. Cancer Chemother.Pharmacol., 2009, 64, 35-43.
223. Smith, N.F.; Baker, S.D.; Gonzalez, F.J.; Harris, J.W.; Figg, W.D.; Sparreboom, A. Modulation of erlotinib pharmacokinetics in miceby a novel cytochrome P450 3A4 inhibitor, BAS 100. Br J Cancer,2008, 98, 1630-1632.
224. Sharma, P.S.; Sharma, R.; Tyagi, T. Receptor tyrosine kinase in-hibitors as potent weapons in war against cancers. Curr. Pharm.Des., 2009, 15, 758-776.
225. Reck, M. Gefitinib in the treatment of advanced non-small-celllung cancer. Expert Rev. Anticancer Ther., 2009, 9, 401-412.
226. Swaisland, H.C.; Smith, R.P.; Laight, A.; Kerr, D.J.; Ranson, M.; Wilder-Smith, C.H.; Duvauchelle, T. Single-dose clinical pharmacokinetic studies of gefitinib. Clin. Pharmacokinet., 2005, 44,1165-1177.
227. McKillop, D.; McCormick, A.D.; Miles, G.S.; Phillips, P.J.; Pickup, K.J.; Bushby, N.; Hutchison, M. In vitro metabolism of ge-fitinib in human liver microsomes. Xenobiotica, 2004, 34, 983-1000.
228. McKillop, D.; Hutchison, M.; Partridge, E.A.; Bushby, N.; Cooper, C.M.; Clarkson-Jones, J.A.; Herron, W.; Swaisland, H.C. Meta-bolic disposition of gefitinib, an epidermal growth factor receptortyrosine kinase inhibitor, in rat, dog and man. Xenobiotica, 2004,34, 917-934.
229. McKillop, D.; Guy, S.P.; Spence, M.P.; Kendrew, J.; Kemp, J.V.; Bushby, N.; Wood, P.G.; Barnett, S.; Hutchison, M. Minimal con-tribution of desmethyl-gefitinib, the major human plasma metabo-lite of gefitinib, to epidermal growth factor receptor (EGFR)-mediated tumour growth inhibition. Xenobiotica, 2006, 36, 29-39.
230. McKillop, D.; McCormick, A.D.; Millar, A.; Miles, G.S.; Phillips, P.J.; Hutchison, M. Cytochrome P450-dependent metabolism ofgefitinib. Xenobiotica, 2005, 35, 39-50.
231. Swaisland, H.C.; Ranson, M.; Smith, R.P.; Leadbetter, J.; Laight, A.; McKillop, D.; Wild, M.J. Pharmacokinetic drug interactions ofgefitinib with rifampicin, itraconazole and metoprolol. Clin. Phar-macokinet., 2005, 44, 1067-1081.
232. Cohen, M.H.; Williams, G.A.; Sridhara, R.; Chen, G.; Pazdur, R. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist, 2003, 8, 303-306.
233. Rau, T.; Wuttke, H.; Michels, L.M.; Werner, U.; Bergmann, K.; Kreft, M.; Fromm, M.F.; Eschenhagen, T. Impact of the CYP2D6genotype on the clinical effects of metoprolol: a prospective longi-tudinal study. Clin. Pharmacol. Ther., 2009, 85, 269-272.
234. Goryachkina, K.; Burbello, A.; Boldueva, S.; Babak, S.; Bergman, U.; Bertilsson, L. CYP2D6 is a major determinant of metoprololdisposition and effects in hospitalized Russian patients treated foracute myocardial infarction. Eur. J. Clin. Pharmacol., 2008, 64,1163-1173.
235. Johnson, J.A.; Burlew, B.S. Metoprolol metabolism via cyto-chrome P4502D6 in ethnic populations. Drug Metab. Dispos.,1996, 24, 350-355.
236. Fulton, B.; Spencer, C.M. Docetaxel. A review of its pharmacody-namic and pharmacokinetic properties and therapeutic efficacy inthe management of metastatic breast cancer. Drugs, 1996, 51,1075-1092.
237. Ramaswamy, B.; Puhalla, S. Docetaxel: a tubulin-stabilizing agentapproved for the management of several solid tumors. Drugs Today(Barc), 2006, 42, 265-279.
238. Saloustros, E.; Mavroudis, D.; Georgoulias, V. Paclitaxel and do-cetaxel in the treatment of breast cancer. Expert Opin. Pharmacother., 2008, 9, 2603-2616.
239. Blagden, S.P.; Kaye, S.B. Docetaxel in the management of ovariancancer. Expert Rev. Anticancer Ther., 2005, 5, 203-214.
240. Bruno, R.; Sanderink, G.J. Pharmacokinetics and metabolism ofTaxotere (docetaxel). Cancer Surv., 1993, 17, 305-313.
241. Marre, F.; Sanderink, G.J.; de Sousa, G.; Gaillard, C.; Martinet, M.; Rahmani, R. Hepatic biotransformation of docetaxel (Taxotere) invitro: involvement of the CYP3A subfamily in humans. CancerRes., 1996, 56, 1296-1302.
242. Engels, F.K.; Loos, W.J.; Mathot, R.A.; van Schaik, R.H.; Verweij, J. Influence of ketoconazole on the fecal and urinary disposition ofdocetaxel. Cancer Chemother. Pharmacol., 2007, 60, 569-579.
243. van Zuylen, L.; Verweij, J.; Nooter, K.; Brouwer, E.; Stoter, G.; Sparreboom, A. Role of intestinal P-glycoprotein in the plasma andfecal disposition of docetaxel in humans. Clin. Cancer Res., 2000,6, 2598-2603.
244. Hopper-Borge, E.; Chen, Z.S.; Shchaveleva, I.; Belinsky, M.G.; Kruh, G.D. Analysis of the drug resistance profile of multidrug re-sistance protein 7 (ABCC10): resistance to docetaxel. Cancer Res.,2004, 64, 4927-4930.
245. Smith, N.F.; Acharya, M.R.; Desai, N.; Figg, W.D.; Sparreboom, A. Identification of OATP1B3 as a high-affinity hepatocellulartransporter of paclitaxel. Cancer Biol. Ther., 2005, 4, 815-818.
246. Cox, M.C.; Low, J.; Lee, J.; Walshe, J.; Denduluri, N.; Berman, A.; Permenter, M.G.; Petros, W.P.; Price, D.K.; Figg, W.D.; Sparreboom, A.; Swain, S.M. Influence of garlic (Allium sativum) on thepharmacokinetics of docetaxel. Clin. Cancer Res., 2006, 12, 4636-4640.
247. Hande, K.R. Etoposide: four decades of development of a topoi-somerase II inhibitor. Eur. J. Cancer, 1998, 34, 1514-1521.
248. Clark, P.I.; Slevin, M.L. The clinical pharmacology of etoposideand teniposide. Clin. Pharmacokinet., 1987, 12, 223-252.
249. Relling, M.V.; Nemec, J.; Schuetz, E.G.; Schuetz, J.D.; Gonzalez, F.J.; Korzekwa, K.R. O-demethylation of epipodophyllotoxins iscatalyzed by human cytochrome P450 3A4. Mol. Pharmacol.,1994, 45, 352-358.
250. Kawashiro, T.; Yamashita, K.; Zhao, X.J.; Koyama, E.; Tani, M.; Chiba, K.; Ishizaki, T. A study on the metabolism of etoposide andpossible interactions with antitumor or supporting agents by humanliver microsomes. J. Pharmacol. Exp. Ther., 1998, 286, 1294-1300.
251. Lum, B.L.; Kaubisch, S.; Yahanda, A.M.; Adler, K.M.; Jew, L.; Ehsan, M.N.; Brophy, N.A.; Halsey, J.; Gosland, M.P.; Sikic, B.I. Alteration of etoposide pharmacokinetics and pharmacodynamicsby cyclosporine in a Phase I trial to modulate multidrug resistance. J. Clin. Oncol., 1992, 10, 1635-1642.
252. Bisogno, G.; Cowie, F.; Boddy, A.; Thomas, H.D.; Dick, G.; Pink-erton, C.R. High-dose cyclosporin with etoposide toxicity andpharmacokinetic interaction in children with solid tumours. Br. J.Cancer, 1998, 77, 2304-2309.
253. You, B.; Tranchand, B.; Girard, P.; Falandry, C.; Ribba, B.; Cha-baud, S.; Souquet, P.J.; Court-Fortune, I.; Trillet-Lenoir, V.; Fournel, C.; Tod, M.; Freyer, G. Etoposide pharmacokinetics andsurvival in patients with small cell lung cancer: a multicentre study. Lung Cancer, 2008, 62, 261-272.
254. Corona, G.; Aita, P.; Sorio, R.; Colussi, A.M.; Bearz, A.; Sartor, F.; Boiocchi, M.; Toffoli, G. Pharmacokinetic interaction betweenetoposide and tamoxifen in patients with hepatocellular carcinoma. Anticancer Drugs, 1999, 10, 815-819.
255. Thomas, H.D.; Porter, D.J.; Bartelink, I.; Nobbs, J.R.; Cole, M.; Elliott, S.; Newell, D.R.; Calvert, A.H.; Highley, M.; Boddy, A.V. Randomized cross-over clinical trial to study potential pharma-cokinetic interactions between cisplatin or carboplatin andetoposide. Br. J. Clin. Pharmacol., 2002, 53, 83-91.
256. Wen, Z.; Tallman, M.N.; Ali, S.Y.; Smith, P.C. UDP-glucuronosyltransferase 1A1 is the principal enzyme responsiblefor etoposide glucuronidation in human liver and intestinal micro-somes: structural characterization of phenolic and alcoholic glucu-ronides of etoposide and estimation of enzyme kinetics. Drug Me-tab. Dispos., 2007, 35, 371-380.
257. Watanabe, Y.; Nakajima, M.; Ohashi, N.; Kume, T.; Yokoi, T. Glucuronidation of etoposide in human liver microsomes is specifi-cally catalyzed by UDP-glucuronosyltransferase 1A1. Drug Metab.Dispos., 2003, 31, 589-595.
258. Reif, S.; Nicolson, M.C.; Bisset, D.; Reid, M.; Kloft, C.; Jaehde, U.; McLeod, H.L. Effect of grapefruit juice intake on etoposidebioavailability. Eur. J. Clin. Pharmacol., 2002, 58, 491-494.
259. Kane, G.C.; Lipsky, J.J. Drug-grapefruit juice interactions. MayoClin. Proc., 2000, 75, 933-942.
260. Bressler, R. Grapefruit juice and drug interactions. Exploringmechanisms of this interaction and potential toxicity for certaindrugs. Geriatrics, 2006, 61, 12-18.
261. Hukkanen, J.; Jacob, P., 3rd; Benowitz, N.L. Effect of grapefruitjuice on cytochrome P450 2A6 and nicotine renal clearance. Clin. Pharmacol. Ther., 2006, 80, 522-530.
262. Bailey, D.G.; Dresser, G.R.; Kreeft, J.H.; Munoz, C.; Freeman, D.J.; Bend, J.R. Grapefruit-felodipine interaction: effect of unproc-essed fruit and probable active ingredients. Clin. Pharmacol. Ther.,2000, 68, 468-477.
263. Vincent, J.; Harris, S.I.; Foulds, G.; Dogolo, L.C.; Willavize, S.; Friedman, H.L. Lack of effect of grapefruit juice on the pharma-cokinetics and pharmacodynamics of amlodipine. Br. J. Clin.Pharmacol., 2000, 50, 455-463.
264. Becquemont, L.; Verstuyft, C.; Kerb, R.; Brinkmann, U.; Lebot, M.; Jaillon, P.; Funck-Brentano, C. Effect of grapefruit juice on di-goxin pharmacokinetics in humans. Clin. Pharmacol. Ther., 2001,70, 311-316.
265. Manthey, J.A.; Buslig, B.S. Distribution of furanocoumarins ingrapefruit juice fractions. J. Agric. Food Chem., 2005, 53, 5158-5163.
266. Baumgart, A.; Schmidt, M.; Schmitz, H.J.; Schrenk, D. Naturalfurocoumarins as inducers and inhibitors of cytochrome P450 1A1in rat hepatocytes. Biochem. Pharmacol., 2005, 69, 657-667.
267. Lim, H.K.; Duczak, N., Jr.; Brougham, L.; Elliot, M.; Patel, K.; Chan, K. Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, andCYP1A2 in pooled human liver microsomes. Drug Metab. Dispos., 2005, 33, 1211-1219.
268. Bumpus, N.N.; Sridar, C.; Kent, U.M.; Hollenberg, P.F. The natu-rally occurring cytochrome P450 (P450) 2B6 K262R mutant ofP450 2B6 exhibits alterations in substrate metabolism and inactivation. Drug Metab. Dispos., 2005, 33, 795-802.
269. Lin, H.L.; Kent, U.M.; Hollenberg, P.F. The grapefruit juice effectis not limited to cytochrome P450 (P450) 3A4: evidence for ber-gamottin-dependent inactivation, heme destruction, and covalentbinding to protein in P450s 2B6 and 3A5. J. Pharmacol. Exp.Ther., 2005, 313, 154-164.
270. Oda, K.; Yamaguchi, Y.; Yoshimura, T.; Wada, K.; Nishizono, N. Synthetic models related to furanocoumarin-CYP 3A4 interactions.comparison of furanocoumarin, coumarin, and benzofuran dimersas potent inhibitors of CYP3A4 activity. Chem. Pharm. Bull. (To-kyo), 2007, 55, 1419-1421.
271. Kakar, S.M.; Paine, M.F.; Stewart, P.W.; Watkins, P.B. 6'7'-Dihydroxybergamottin contributes to the grapefruit juice effect. Clin. Pharmacol. Ther., 2004, 75, 569-579.
272. He, K.; Iyer, K.R.; Hayes, R.N.; Sinz, M.W.; Woolf, T.F.; Hollen-berg, P.F. Inactivation of cytochrome P450 3A4 by bergamottin, acomponent of grapefruit juice. Chem. Res. Toxicol., 1998, 11, 252-259.
273. Wangensteen, H.; Molden, E.; Christensen, H.; Malterud, K.E. Identification of epoxybergamottin as a CYP3A4 inhibitor ingrapefruit peel. Eur. J. Clin. Pharmacol., 2003, 58, 663-668.
274. Rooseboom, M.; Commandeur, J.N.; Vermeulen, N.P. Enzyme-catalyzed activation of anticancer prodrugs. Pharmacol. Rev., 2004,56, 53-102.
275. Whitten, D.L.; Myers, S.P.; Hawrelak, J.A.; Wohlmuth, H. Theeffect of St John's wort extracts on CYP3A: a systematic review ofprospective clinical trials. Br. J. Clin. Pharmacol., 2006, 62, 512-526.
276. Madabushi, R.; Frank, B.; Drewelow, B.; Derendorf, H.; Butter-weck, V. Hyperforin in St. John's wort drug interactions. Eur. J.Clin. Pharmacol., 2006, 62, 225-233.
277. Zhou, S.F.; Lai, X. An update on clinical drug interactions with theherbal antidepressant St. John's wort. Curr. Drug Metab., 2008, 9,394-409.
278. Dresser, G.K.; Schwarz, U.I.; Wilkinson, G.R.; Kim, R.B. Coordi-nate induction of both cytochrome P4503A and MDR1 by St John'swort in healthy subjects. Clin. Pharmacol. Ther., 2003, 73, 41-50.
279. Di, Y.M.; Li, C.G.; Xue, C.C.; Zhou, S.F. Clinical drugs that inter-act with St. John's wort and implication in drug development. Curr. Pharm. Des., 2008, 14, 1723-1742.
280. Dean, M.; Rzhetsky, A.; Allikmets, R. The human ATP-bindingcassette (ABC) transporter superfamily. Genome Res., 2001, 11,1156-1166.
281. Sarkadi, B.; Homolya, L.; Szakacs, G.; Varadi, A. Humanmultidrug resistance ABCB and ABCG transporters: participationin a chemoimmunity defense system. Physiol. Rev., 2006, 86,1179-1236.
282. Wakabayashi, K.; Tamura, A.; Saito, H.; Onishi, Y.; Ishikawa, T. Human ABC transporter ABCG2 in xenobiotic protection and re-dox biology. Drug Metab. Rev., 2006, 38, 371-391.
283. Tian, Q.; Zhang, J.; Chan, S.Y.; Tan, T.M.; Duan, W.; Huang, M.; Zhu, Y.Z.; Chan, E.; Yu, Q.; Nie, Y.Q.; Ho, P.C.; Li, Q.; Ng, K.Y.; Yang, H.Y.; Wei, H.; Bian, J.S.; Zhou, S.F. Topotecan is a sub-strate for multidrug resistance associated protein 4. Curr. Drug Metab., 2006, 7, 105-118.
284. Sharom, F.J. ABC multidrug transporters: structure, function androle in chemoresistance. Pharmacogenomics, 2008, 9, 105-127.
285. Noguchi, K.; Katayama, K.; Mitsuhashi, J.; Sugimoto, Y. Functionsof the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv. Drug Deliv. Rev., 2009, 61, 26-33.
286. Marchetti, S.; Oostendorp, R.L.; Pluim, D.; van Eijndhoven, M.; van Tellingen, O.; Schinkel, A.H.; Versace, R.; Beijnen, J.H.; Maz-zanti, R.; Schellens, J.H. In vitro transport of gimatecan (7-t-butoxyiminomethylcamptothecin) by breast cancer resistance pro-tein, P-glycoprotein, and multidrug resistance protein 2. Mol. Cancer Ther., 2007, 6, 3307-3313.
287. Priebe, W.; Krawczyk, M.; Kuo, M.T.; Yamane, Y.; Savaraj, N.; Ishikawa, T. Doxorubicin- and daunorubicin-glutathione conjugates, but not unconjugated drugs, competitively inhibit leukotrieneC4 transport mediated by MRP/GS-X pump. Biochem. Biophys. Res. Commun., 1998, 247, 859-863.
288. Sakamoto, H.; Hara, H.; Hirano, K.; Adachi, T. Enhancement ofglucuronosyl etoposide transport by glutathione in multidrug resis-tance-associated protein-overexpressing cells. Cancer Lett., 1999,135, 113-119.
289. Cui, Y.; Konig, J.; Buchholz, J.K.; Spring, H.; Leier, I.; Keppler, D. Drug resistance and ATP-dependent conjugate transport mediatedby the apical multidrug resistance protein, MRP2, permanently ex-pressed in human and canine cells. Mol. Pharmacol., 1999, 55,929-937.
290. Kawabe, T.; Chen, Z.S.; Wada, M.; Uchiumi, T.; Ono, M.; Aki-yama, S.; Kuwano, M. Enhanced transport of anticancer agents andleukotriene C4 by the human canalicular multispecific organic an-ion transporter (cMOAT/MRP2). FEBS Lett., 1999, 456, 327-331.
291. Kool, M.; van der Linden, M.; de Haas, M.; Scheffer, G.L.; deVree, J.M.; Smith, A.J.; Jansen, G.; Peters, G.J.; Ponne, N.; Scheper, R.J.; Elferink, R.P.; Baas, F.; Borst, P. MRP3, an organicanion transporter able to transport anticancer drugs. Proc. Natl.Acad. Sci. U. S. A., 1999, 96, 6914-6919.
292. Chen, Z.S.; Lee, K.; Kruh, G.D. Transport of cyclic nucleotides andestradiol 17-D-glucuronide by multidrug resistance protein 4.Resistance to 6-mercaptopurine and 6-thioguanine. J. Biol. Chem.,2001, 276, 33747-33754.
293. Jedlitschky, G.; Burchell, B.; Keppler, D. The multidrug resistanceprotein 5 functions as an ATP-dependent export pump for cyclicnucleotides. J. Biol. Chem., 2000, 275, 30069-30074.
294. Oguri, T.; Bessho, Y.; Achiwa, H.; Ozasa, H.; Maeno, K.; Maeda, H.; Sato, S.; Ueda, R. MRP8/ABCC11 directly confers resistanceto 5-fluorouracil. Mol. Cancer Ther., 2007, 6, 122-127.
295. Hennessy, M.; Kelleher, D.; Spiers, J.P.; Barry, M.; Kavanagh, P.; Back, D.; Mulcahym, F.; Feely, J. St John's wort increases expres-sion of P-glycoprotein: implications for drug interactions. Br. J.Clin. Pharmacol., 2002, 53, 75-82.
296. Perloff, M.D.; von Moltke, L.L.; Stormer, E.; Shader, R.I.; Green-blatt, D.J. Saint John's wort: an in vitro analysis of P-glycoproteininduction due to extended exposure. Br. J. Pharmacol., 2001, 134,1601-1608.
297. Durr, D.; Stieger, B.; Kullak-Ublick, G.A.; Rentsch, K.M.; Steinert, H.C.; Meier, P.J.; Fattinger, K. St John's wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin.Pharmacol. Ther., 2000, 68, 598-604.
298. Xie, R.; Tan, L.H.; Polasek, E.C.; Hong, C.; Teillol-Foo, M.; Gordi, T.; Sharma, A.; Nickens, D.J.; Arakawa, T.; Knuth, D.W.; Antal, E.J. CYP3A and P-glycoprotein activity induction with St.John's wort in healthy volunteers from 6 ethnic populations. J. Clin. Pharmacol., 2005, 45, 352-356.
299. Lehmann, J.M.; McKee, D.D.; Watson, M.A.; Willson, T.M.; Moore, J.T.; Kliewer, S.A. The human orphan nuclear receptorPXR is activated by compounds that regulate CYP3A4 gene expres-sion and cause drug interactions. J. Clin. Invest., 1998, 102, 1016-1023.
300. Goodwin, B.; Redinbo, M.R.; Kliewer, S.A. Regulation of CYP3Agene transcription by the pregnane X receptor. Annu. Rev. Pharmacol. Toxicol., 2002, 42, 1-23.
301. Zhou, S.; Chan, E.; Li, S.C.; Huang, M.; Chen, X.; Li, X.; Zhang, Q.; Paxton, J.W. Predicting pharmacokinetic herb-drug interac-tions. Drug Metabol. Drug Interact., 2004, 20, 143-158.
302. Itoh, M.; Nakajima, M.; Higashi, E.; Yoshida, R.; Nagata, K.; Ya-mazoe, Y.; Yokoi, T. Induction of human CYP2A6 is mediated bythe pregnane X receptor with peroxisome proliferator-activatedreceptor-coactivator 1. J. Pharmacol. Exp. Ther., 2006, 319,693-702.
303. Sinz, M.; Kim, S.; Zhu, Z.; Chen, T.; Anthony, M.; Dickinson, K.; Rodrigues, A.D. Evaluation of 170 xenobiotics as transactivators ofhuman pregnane X receptor (hPXR) and correlation to knownCYP3A4 drug interactions. Curr. Drug Metab., 2006, 7, 375-388.
304. Orans, J.; Teotico, D.G.; Redinbo, M.R. The nuclear xenobioticreceptor pregnane X receptor: recent insights and new challenges. Mol. Endocrinol., 2005, 19, 2891-2900.
305. Zhou, S.F.; Zhou, Z.W.; Li, C.G.; Chen, X.; Yu, X.; Xue, C.C.; Herington, A. Identification of drugs that interact with herbs indrug development. Drug Discov. Today, 2007, 12, 664-673.
306. Barton, D.L.; Soori, G.S.; Bauer, B.A.; Sloan, J.A.; Johnson, P.A.; Figueras, C.; Duane, S.; Mattar, B.; Liu, H.; Atherton, P.J.; Christensen, B.; Loprinzi, C.L. Pilot study of Panax quinquefolius(American ginseng) to improve cancer-related fatigue: a random-ized, double-blind, dose-finding evaluation: NCCTG trial N03CA.Support. Care Cancer, 2009, 18, 179-187.
307. Seely, D.; Kennedy, D.A.; Myers, S.P.; Cheras, P.A.; Lin, D.; Li,R.; Cattley, T.; Brent, P.A.; Mills, E.; Leonard, B.J. In vitro analy-sis of the herbal compound Essiac. Anticancer Res., 2007, 27,3875-3882.
308. Qin, Z. F.; Wei, P. K.; Li, J. [Effect of kanglaite injection combinedwith Chinese drug therapy according to syndrome differentiationon quality of life and immune function in patients with advancedlung cancer]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2002, 22, 618-619.
309. Deng, S.G.; Wen, S.B.; Chen, A.L. Clinical observation ofKanglaite injection combined with gemzar and carboplatin in thetreatment of middle and late stage NSCLC. Zhejiang Pract Med,2006, 11, 234-236.
310. Sood, A.; Barton, D.L.; Bauer, B.A.; Loprinzi, C.L. A critical review of complementary therapies for cancer-related fatigue. Integr.Cancer Ther., 2007, 6, 8-13.
311. Lee, Y.J.; Chung, H.Y.; Kwak, H.K.; Yoon, S. The effects of A.senticosus supplementation on serum lipid profiles, biomarkers ofoxidative stress, and lymphocyte DNA damage in postmenopausalwomen. Biochem. Biophys. Res. Commun., 2008, 375, 44-48.
312. Donovan, J.L.; DeVane, C.L.; Chavin, K.D.; Taylor, R.M.; Mark-owitz, J.S. Siberian ginseng (Eleutheroccus senticosus) effects onCYP2D6 and CYP3A4 activity in normal volunteers. Drug Metab.Dispos., 2003, 31, 519-522.
313. Kuffel, M.J.; Schroeder, J.C.; Pobst, L.J.; Naylor, S.; Reid, J.M.; Kaufmann, S.H.; Ames, M.M. Activation of the antitumor agentaminoflavone (NSC 686288) is mediated by induction of tumor cellcytochrome P450 1A1/1A2. Mol. Pharmacol., 2002, 62, 143-153.
314. Chen, C.; Meng, L.; Ma, X.; Krausz, K.W.; Pommier, Y.; Idle, J.R.; Gonzalez, F.J. Urinary metabolite profiling reveals CYP1A2-mediated metabolism of NSC686288 (aminoflavone). J. Pharma-col. Exp. Ther., 2006, 318, 1330-1342.
315. Brandon, E.F.; Sparidans, R.W.; van Ooijen, R.D.; Meijerman, I.; Lazaro, L.L.; Manzanares, I.; Beijnen, J.H.; Schellens, J.H. In vitrocharacterization of the human biotransformation pathways ofaplidine, a novel marine anticancer drug. Invest. New Drugs, 2007,25, 9-19.
316. Kamath, A.V.; Chang, M.; Lee, F.Y.; Zhang, Y.; Marathe, P.H.Preclinical pharmacokinetics and oral bioavailability of BMS-310705, a novel epothilone B analog. Cancer Chemother. Pharmacol., 2005, 56, 145-153.
317. Pekol, T.; Daniels, J.S.; Labutti, J.; Parsons, I.; Nix, D.; Baronas, E.; Hsieh, F.; Gan, L.S.; Miwa, G. Human metabolism of the pro-teasome inhibitor bortezomib: identification of circulating metabolites. Drug Metab. Dispos., 2005, 33, 771-777.
318. Uttamsingh, V.; Lu, C.; Miwa, G.; Gan, L.S. Relative contributionsof the five major human cytochromes P450, 1A2, 2C9, 2C19, 2D6,and 3A4, to the hepatic metabolism of the proteasome inhibitorbortezomib. Drug Metab. Dispos., 2005, 33, 1723-1728.
319. Zhang, J.; Tian, Q.; Yung Chan, S.; Chuen Li, S.; Zhou, S.; Duan, W.; Zhu, Y.Z. Metabolism and transport of oxazaphosphorines andthe clinical implications. Drug Metab. Rev., 2005, 37, 611-703.
320. Zhang, J.; Tian, Q.; Chan, S.Y.; Duan, W.; Zhou, S. Insights intooxazaphosphorine resistance and possible approaches to its circumvention. Drug Resist. Updat., 2005, 8, 271-297.
321. Zhang, J.; Tian, Q.; Zhou, S.F. Clinical pharmacology of cyclo-phosphamide and ifosfamide. Curr. Drug Ther., 2006, 1, 104-168.
322. 6-benzylguanine: implications for dacarbazine activation. Clin. Cancer Res., 2001, 7, 4239-4244.
323. Reid, J.M.; Kuffel, M.J.; Miller, J.K.; Rios, R.; Ames, M.M. Meta-bolic activation of dacarbazine by human cytochromes P450: therole of CYP1A1, CYP1A2, and CYP2E1. Clin. Cancer Res., 1999,5, 2192-2197.
324. Storme, T.; Deroussent, A.; Mercier, L.; Prost, E.; Re, M.; Munier, F.; Martens, T.; Bourget, P.; Vassal, G.; Royer, J.; Paci, A. Newifosfamide analogs designed for lower associated neurotoxicity andnephrotoxicity with modified alkylating kinetics leading to enhanced in vitro anticancer activity. J. Pharmacol. Exp. Ther., 2009,328, 598-609.
325. Zhou, S.; Paxton, J.W.; Tingle, M.D.; Kestell, P. Identification ofthe human liver cytochrome P450 isoenzyme responsible for the 6-methylhydroxylation of the novel anticancer drug 5,6-dimethylxanthenone-4-acetic acid. Drug Metab. Dispos., 2000, 28,1449-1456.
326. Royer, I.; Monsarrat, B.; Sonnier, M.; Wright, M.; Cresteil, T. Metabolism of docetaxel by human cytochromes P450: interactionswith paclitaxel and other antineoplastic drugs. Cancer Res., 1996,56, 58-65.
327. Le Guellec, C.; Lacarelle, B.; Catalin, J.; Durand, A. Inhibitoryeffects of anticancer drugs on dextromethorphan-O-demethylaseactivity in human liver microsomes. Cancer Chemother. Pharmacol., 1993, 32, 491-495.
328. Stiborova, M.; Arlt, V.M.; Henderson, C.J.; Wolf, C.R.; Kotrbova, V.; Moserova, M.; Hudecek, J.; Phillips, D.H.; Frei, E. Role of hepatic cytochromes P450 in bioactivation of the anticancer drug ellipticine: studies with the hepatic NADPH:cytochrome P450 reductase null mouse. Toxicol. Appl. Pharmacol., 2008, 226, 318-327.
329. Aimova, D.; Svobodova, L.; Kotrbova, V.; Mrazova, B.; Hodek, P.; Hudecek, J.; Vaclavikova, R.; Frei, E.; Stiborova, M. The anticancer drug ellipticine is a potent inducer of rat cytochromes P4501A1 and 1A2, thereby modulating its own metabolism. Drug Metab. Dispos., 2007, 35, 1926-1934.
330. Zhuo, X.; Zheng, N.; Felix, C.A.; Blair, I.A. Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab. Dispos., 2004, 32, 993-1000.
331. Zheng, N.; Pang, S.; Oe, T.; Felix, C.A.; Wehrli, S.; Blair, I.A. Characterization of an etoposide-glutathione conjugate derivedfrom metabolic activation by human cytochrome P450. Curr. DrugMetab., 2006, 7, 897-911.
332. Roy, P.; Tretyakov, O.; Wright, J.; Waxman, D.J. Stereoselectivemetabolism of ifosfamide by human P-450s 3A4 and 2B6. Favor-able metabolic properties of Renantiomer. Drug Metab. Dispos.,1999, 27, 1309-1318.
333. Granvil, C.P.; Madan, A.; Sharkawi, M.; Parkinson, A.; Wainer, I.W. Role of CYP2B6 and CYP3A4 in the in vitro N-dechloroethylation of (R)- and (S)-ifosfamide in human liver mi-crosomes. Drug Metab. Dispos., 1999, 27, 533-541.
334. Zandvliet, A.S.; Huitema, A.D.; Copalu, W.; Yamada, Y.; Tamura, T.; Beijnen, J.H.; Schellens, J.H. CYP2C9 and CYP2C19 polymor-phic forms are related to increased indisulam exposure and higherrisk of severe hematologic toxicity. Clin. Cancer Res., 2007, 13,2970-2976.
335. Rivory, L.P.; Haaz, M.C.; Canal, P.; Lokiec, F.; Armand, J.P.; Robert, J. Pharmacokinetic interrelationships of irinotecan (CPT-11) and its three major plasma metabolites in patients enrolled inPhase I/II trials. Clin. Cancer Res., 1997, 3, 1261-1266.
336. Rivory, L.P.; Bowles, M.R.; Robert, J.; Pond, S.M. Conversion ofirinotecan (CPT-11) to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), by human liver carboxylesterase. Biochem. Pharmacol., 1996, 52, 1103-1111.
337. Haaz, M.C.; Rivory, L.; Riche, C.; Vernillet, L.; Robert, J. Metabolism of irinotecan (CPT-11) by human hepatic microsomes: participation of cytochrome P-450 3A and drug interactions. Cancer Res,1998, 58, 468-472.
338. Sai, K.; Kaniwa, N.; Ozawa, S.; Sawada, J.I. A new metabolite ofirinotecan in which formation is mediated by human hepatic cytochrome P-450 3A4. Drug Metab. Dispos., 2001, 29, 1505-1513.
339. Nassar, A.F.; King, I.; Paris, B.L.; Haupt, L.; Ndikum-Moffor, F.; Campbell, R.; Usuki, E.; Skibbe, J.; Brobst, D.; Ogilvie, B.W.; Parkinson, A. An in vitro evaluation of the victim and perpetratorpotential of the anticancer agent laromustine (VNP40101M),based on reaction phenotyping and inhibition and induction of cytochrome P450 (CYP) enzymes. Drug Metab. Dispos., 2009, 37,1922-1930.
340. Lu, H.; Waxman, D.J. Antitumor activity of methoxymorpholinyldoxorubicin: potentiation by cytochrome P450 3A metabolism. Mol. Pharmacol., 2005, 67, 212-219.
341. Valles, B.; Schiller, C.D.; Coassolo, P.; De Sousa, G.; Wyss, R.; Jaeck, D.; Viger-Chougnet, A.; Rahmani, R. Metabolism of mofarotene in hepatocytes and liver microsomes from different species. Comparison with in vivo data and evaluation of the cytochrome P450 isoenzymes involved in human biotransformation. Drug Metab. Dispos., 1995, 23, 1051-1057.
342. Quintieri, L.; Geroni, C.; Fantin, M.; Battaglia, R.; Rosato, A.; Speed, W.; Zanovello, P.; Floreani, M. Formation and antitumoractivity of PNU-159682, a major metabolite of nemorubicin in hu-man liver microsomes. Clin. Cancer Res., 2005, 11, 1608-1617.
343. Guns, E.S.; Bullock, P.L.; Reimer, M.L.; Dixon, R.; Bally, M.; Mayer, L.D. Assessment of the involvement of CYP3A in in vitrometabolism of a new modulator of MDR in cancer chemotherapy,OC144-193, by human liver microsomes. Eur. J. Drug Metab. Pharmacokinet., 2001, 26, 273-282.
344. Medower, C.; Wen, L.; Johnson, W.W. Cytochrome P450 oxidation of the thiophene-containing anticancer drug 3-[(quinolin-4-ylmethyl)-amino]-thiophene-2-carboxylic acid (4-trifluorome-thoxy-phenyl)-amide to an electrophilic intermediate. Chem. Res.Toxicol., 2008, 21, 1570-1577.
345. Desai, P.B.; Duan, J.Z.; Zhu, Y.W.; Kouzi, S. Human liver microsomal metabolism of paclitaxel and drug interactions. Eur. J. DrugMetab. Pharmacokinet., 1998, 23, 417-424.
346. Martinez, C.; Garcia-Martin, E.; Pizarro, R.M.; Garcia-Gamito, F.J.; Agundez, J.A. Expression of paclitaxel-inactivating CYP3Aactivity in human colorectal cancer: implications for drug therapy.Br. J. Cancer, 2002, 87, 681-686.
347. McClue, S.J.; Stuart, I. Metabolism of the trisubstituted purinecyclin-dependent kinase inhibitor seliciclib (R-roscovitine) in vitroand in vivo. Drug Metab. Dispos., 2008, 36, 561-570.
348. Keating, G.M.; Santoro, A. Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs, 2009, 69, 223-240.
349. Beverage, J.N.; Sissung, T.M.; Sion, A.M.; Danesi, R.; Figg, W.D. CYP2D6 polymorphisms and the impact on tamoxifen therapy. J.Pharm. Sci., 2007, 96, 2224-2231.
350. Stearns, V.; Johnson, M.D.; Rae, J.M.; Morocho, A.; Novielli, A.; Bhargava, P.; Hayes, D.F.; Desta, Z.; Flockhart, D.A. Active tamoxifen metabolite plasma concentrations after coadministration oftamoxifen and the selective serotonin reuptake inhibitor paroxetine.J. Natl. Cancer Inst., 2003, 95, 1758-1764.
351. Crewe, H.K.; Notley, L.M.; Wunsch, R.M.; Lennard, M.S.; Gillam, E.M. Metabolism of tamoxifen by recombinant human cytochromeP450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab. Dispos., 2002, 30, 869-874.
352. Dehal, S.S.; Kupfer, D. CYP2D6 catalyzes tamoxifen 4-hydroxylation in human liver. Cancer Res., 1997, 57, 3402-3406.
353. Ikeda, K.; Yoshisue, K.; Matsushima, E.; Nagayama, S.; Kobaya-shi, K.; Tyson, C.A.; Chiba, K.; Kawaguchi, Y. Bioactivation oftegafur to 5-fluorouracil is catalyzed by cytochrome P450 2A6 inhuman liver microsomes in vitro. Clin. Cancer Res., 2000, 6, 4409-4415.
354. Komatsu, T.; Yamazaki, H.; Shimada, N.; Nakajima, M.; Yokoi, T. Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracilformation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab. Dispos., 2000, 28, 1457-1463.
355. Komatsu, T.; Yamazaki, H.; Shimada, N.; Nagayama, S.; Kawa-guchi, Y.; Nakajima, M.; Yokoi, T. Involvement of microsomal cytochrome P450 and cytosolic thymidine phosphorylase in 5-fluorouracil formation from tegafur in human liver. Clin. Cancer Res., 2001, 7, 675-681.
356. Kousba, A.; Soll, R.; Yee, S.; Martin, M. Cyclic conversion of thenovel Src kinase inhibitor [7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[4-(2-pyrrolid in-1-yl-ethoxy)-phenyl]-amine (TG100435) and its Noxide metabolite by flavin-containingmonoxygenases and cytochrome P450 reductase. Drug Metab.Dispos., 2007, 35, 2242-2251.
357. Miyata, M.; Tamura, E.; Motoki, K.; Nagata, K.; Yamazoe, Y. Thalidomide-induced suppression of embryo fibroblast prolifera-tion requires CYP1A1-mediated activation. Drug Metab. Dispos.,2003, 31, 469-475.
358. Brandon, E.F.; Sparidans, R.W.; Meijerman, I.; Manzanares, I.; Beijnen, J.H.; Schellens, J.H. In vitro characterization of thebiotransformation of thiocoraline, a novel marine anti-cancer drug. Invest. New Drugs, 2004, 22, 241-251.
359. Sparreboom, A.; Marsh, S.; Mathijssen, R.H.; Verweij, J.; McLeod, H.L. Pharmacogenetics of tipifarnib (R115777) transport and metabolism in cancer patients. Invest. New Drugs, 2004, 22, 285-289.
360. Reid, J.M.; Kuffel, M.J.; Ruben, S.L.; Morales, J.J.; Rinehart, K.L.; Squillace, D.P.; Ames, M.M. Rat and human liver cytochrome P-450 isoform metabolism of ecteinascidin 743 does not predict gen-der-dependent toxicity in humans. Clin. Cancer Res., 2002, 8,2952-2962.
361. Brandon, E.F.; Sparidans, R.W.; Guijt, K.J.; Lowenthal, S.; Mei-jerman, I.; Beijnen, J.H.; Schellens, J.H. In vitro characterization ofthe human biotransformation and CYP reaction phenotype of ET-743 (Yondelis, Trabectidin), a novel marine anti-cancer drug. Invest. New Drugs, 2006, 24, 3-14.
362. Vermeir, M.; Hemeryck, A.; Cuyckens, F.; Francesch, A.; Bockx, M.; Van Houdt, J.; Steemans, K.; Mannens, G.; Aviles, P.; De Coster, R. In vitro studies on the metabolism of trabectedin (Yondelis)in monkey and man, including human CYP reaction phenotyping. Biochem. Pharmacol., 2009, 77, 1642-1654.
363. Kitamura, R.; Asanoma, H.; Nagayama, S.; Otagiri, M. Identifica-tion of human liver cytochrome P450 isoforms involved in autoin-duced metabolism of the antiangiogenic agent (Z)-5-[(1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-propanoic acid (TSU-68). Drug Metab. Dispos., 2008, 36, 1003-1009.
364. Fischer, V.; Rodriguez-Gascon, A.; Heitz, F.; Tynes, R.; Hauck, C.; Cohen, D.; Vickers, A.E. The multidrug resistance modulator valspodar (PSC 833) is metabolized by human cytochrome P450 3A.Implications for drug-drug interactions and pharmacological activ-ity of the main metabolite. Drug Metab. Dispos., 1998, 26, 802-811.
365. Zhou-Pan, X.R.; Seree, E.; Zhou, X.J.; Placidi, M.; Maurel, P.; Barra, Y.; Rahmani, R. Involvement of human liver cytochromeP450 3A in vinblastine metabolism: drug interactions. Cancer Res.,1993, 53, 5121-5126.
366. Yao, D.; Ding, S.; Burchell, B.; Wolf, C.R.; Friedberg, T. Detoxi-cation of vinca alkaloids by human P450 CYP3A4-mediated me-tabolism: implications for the development of drug resistance. J.Pharmacol. Exp. Ther., 2000, 294, 387-395.
367. Dennison, J.B.; Kulanthaivel, P.; Barbuch, R.J.; Renbarger, J.L.; Ehlhardt, W.J.; Hall, S.D. Selective metabolism of vincristine in vi-tro by CYP3A5. Drug Metab. Dispos., 2006, 34, 1317-1327.
368. Zhou, X.J.; Zhou-Pan, X.R.; Gauthier, T.; Placidi, M.; Maurel, P.; Rahmani, R. Human liver microsomal cytochrome P450 3Aisozymes mediated vindesine biotransformation. Metabolic drug interactions. Biochem. Pharmacol., 1993, 45, 853-861.
369. Kajita, J.; Kuwabara, T.; Kobayashi, H.; Kobayashi, S. CYP3A4 ismainly responsibile for the metabolism of a new vinca alkaloid, vinorelbine, in human liver microsomes. Drug Metab. Dispos., 2000,28, 1121-1127.
370. Cheng, Z.; Radominska-Pandya, A.; Tephly, T.R. Studies on thesubstrate specificity of human intestinal UDP-lucuronosy ltransferases 1A8 and 1A10. Drug Metab. Dispos., 1999, 27, 1165-1170.
371. Hoehle, S.I.; Pfeiffer, E.; Metzler, M. Glucuronidation of curcuminoids by human microsomal and recombinant UDP-glucuronosyltransferases. Mol. Nutr. Food Res., 2007, 51, 932-938.
372. Miners, J.O.; Valente, L.; Lillywhite, K.J.; Mackenzie, P.I.; Burchell, B.; Baguley, B.C.; Kestell, P. Preclinical prediction offactors influencing the elimination of 5,6-dimethylxanthenone-4-acetic acid, a new anticancer drug. Cancer Res., 1997, 57, 284-289.
373. Lu, H.; Meng, X.; Li, C.; Sang, S.; Patten, C.; Sheng, S.; Hong, J.; Bai, N.; Winnik, B.; Ho, C.T.; Yang, C.S. Glucuronides of teacatechins: enzymology of biosynthesis and biological activities. Drug Metab. Dispos., 2003, 31, 452-461.
374. Innocenti, F.; Iyer, L.; Ramirez, J.; Green, M.D.; Ratain, M.J. Epirubicin glucuronidation is catalyzed by human UDP-glucuronosyltransferase 2B7. Drug Metab. Dispos., 2001, 29, 686-692.
375. Staines, A.G.; Sindelar, P.; Coughtrie, M.W.; Burchell, B. Farnesolis glucuronidated in human liver, kidney and intestine in vitro, andis a novel substrate for UGT2B7 and UGT1A1. Biochem. J., 2004,384, 637-645.
376. Ramirez, J.; Iyer, L.; Journault, K.; Belanger, P.; Innocenti, F.; Ratain, M.J.; Guillemette, C. In vitro characterization of hepaticflavopiridol metabolism using human liver microsomes and recom-binant UGT enzymes. Pharm. Res., 2002, 19, 588-594.
377. Villeneuve, L.; Girard, H.; Fortier, L.C.; Gagne, J.F.; Guillemette, C. Novel functional polymorphisms in the UGT1A7 and UGT1A9glucuronidating enzymes in Caucasian and African-American subjects and their impact on the metabolism of 7-ethyl-10-hydroxycamptothecin and flavopiridol anticancer drugs. J. Pharmacol. Exp. Ther., 2003, 307, 117-128.
378. Hagenauer, B.; Salamon, A.; Thalhammer, T.; Kunert, O.; Haslinger, E.; Klingler, P.; Senderowicz, A.M.; Sausville, E.A.; Jager, W. In vitro glucuronidation of the cyclin-dependent kinase inhibitorflavopiridol by rat and human liver microsomes: involvement ofUDP-glucuronosyltransferases 1A1 and 1A9. Drug Metab. Dispos.,2001, 29, 407-414.
379. Samokyszyn, V.M.; Gall, W.E.; Zawada, G.; Freyaldenhoven, M.A.; Chen, G.; Mackenzie, P.I.; Tephly, T.R.; Radominska-Pandya, A. 4-Hydroxyretinoic acid, a novel substrate for humanliver microsomal UDP-glucuronosyltransferase(s) and recombinant UGT2B7. J. Biol. Chem., 2000, 275, 6908-6914.
380. Blevins-Primeau, A.S.; Sun, D.; Chen, G.; Sharma, A.K.; Galla-gher, C.J.; Amin, S.; Lazarus, P. Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active ta-moxifen metabolites. Cancer Res., 2009, 69, 1892-1900.
381. Sun, D.; Sharma, A.K.; Dellinger, R.W.; Blevins-Primeau, A.S.; Balliet, R.M.; Chen, G.; Boyiri, T.; Amin, S.; Lazarus, P. Glucuronidation of active tamoxifen metabolites by the human UDP glucuronosyltransferases. Drug Metab. Dispos., 2007, 35, 2006-2014.
382. Sun, D.; Chen, G.; Dellinger, R.W.; Duncan, K.; Fang, J.L.; Lazarus, P. Characterization of tamoxifen and 4-hydroxytamoxifen glucuronidation by human UGT1A4 variants. Breast Cancer Res.,2006, 8, R50.
383. Ogura, K.; Ishikawa, Y.; Kaku, T.; Nishiyama, T.; Ohnuma, T.; Muro, K.; Hiratsuka, A. Quaternary ammonium-linked glucuroni-dation of trans-4-hydroxytamoxifen, an active metabolite of ta-moxifen, by human liver microsomes and UDP-glucuronosyltransferase 1A4. Biochem. Pharmacol., 2006, 71,1358-1369.
384. Jeong, E.J.; Liu, Y.; Lin, H.; Hu, M. Species-and dispositionmodel-dependent metabolism of raloxifene in gut and liver: role ofUGT1A10. Drug Metab. Dispos., 2005, 33, 785-794.
385. Oguri, T.; Takahashi, T.; Miyazaki, M.; Isobe, T.; Kohno, N.; Mackenzie, P.I.; Fujiwara, Y. UGT1A10 is responsible for SN-38 glucuronidation and its expression in human lung cancers. Anticancer Res., 2004, 24, 2893-2896.
386. Nagar, S.; Blanchard, R.L. Pharmacogenetics of uridinediphosphoglucuronosyltransferase (UGT) 1A family members andits role in patient response to irinotecan. Drug Metab. Rev., 2006,38, 393-409.
387. Rosing, H.; van Zomeren, D.M.; Doyle, E.; Bult, A.; Beijnen, J.H. O-Glucuronidation, a newly identified metabolic pathway for topotecan and N-desmethyl topotecan. Anticancer Drugs, 1998, 9, 587-592.
388. Zhou, S.F. Structure, function and regulation of Pglycoprotein andits clinical relevance in drug disposition. Xenobiotica, 2008, 38,802-832.
389. Zhou, S.F.; Xue, C.C.; Yu, X.Q.; Li, C.; Wang, G. Clinically important drug interactions potentially involving mechanism-basedinhibition of cytochrome P450 3A4 and the role of therapeutic drugmonitoring. Ther. Drug Monit., 2007, 29, 687-710.
390. Aller, S.G.; Yu, J.; Ward, A.; Weng, Y.; Chittaboina, S.; Zhuo, R.; Harrell, P.M.; Trinh, Y.T.; Zhang, Q.; Urbatsch, I.L.; Chang, G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science, 2009, 323, 1718-1722.
391. Beumer, J.H.; Buckle, T.; Ouwehand, M.; Franke, N.E.; Lopez-Lazaro, L.; Schellens, J.H.; Beijnen, J.H.; van Tellingen, O. Trabectedin (ET-743, Yondelis) is a substrate for P-glycoprotein, butonly high expression of P-glycoprotein confers the multidrug resistance phenotype. Invest. New Drugs, 2007, 25, 1-7.
392. Ambudkar, S.V.; Kimchi-Sarfaty, C.; Sauna, Z.E.; Gottesman,M.M. P-glycoprotein: from genomics to mechanism. Oncogene,2003, 22, 7468-7485.
393. Sarkadi, B.; Ozvegy-Laczka, C.; Nemet, K.; Varadi, A. ABCG2 atransporter for all seasons. FEBS Lett, 2004, 567, 116-120.
394. Morrow, C.S.; Peklak-Scott, C.; Bishwokarma, B.; Kute, T.E.; Smitherman, P.K.; Townsend, A.J. Multidrug resistance protein 1(MRP1, ABCC1) mediates resistance to mitoxantrone via glu-tathione-dependent drug efflux. Mol. Pharmacol., 2006, 69, 1499-1505.
395. Hooijberg, J.H.; Peters, G.J.; Assaraf, Y.G.; Kathmann, I.; Priest, D.G.; Bunni, M.A.; Veerman, A.J.; Scheffer, G.L.; Kaspers, G.J.; Jansen, G. The role of multidrug resistance proteins MRP1, MRP2and MRP3 in cellular folate homeostasis. Biochem. Pharmacol.,2003, 65, 765-771.
396. Hooijberg, J.H.; Broxterman, H.J.; Kool, M.; Assaraf, Y.G.; Peters, G.J.; Noordhuis, P.; Scheper, R.J.; Borst, P.; Pinedo, H.M.; Jansen, G. Antifolate resistance mediated by the multidrug resistance pro-teins MRP1 and MRP2. Cancer Res., 1999, 59, 2532-2535.
397. Vlaming, M.L.; Pala, Z.; van Esch, A.; Wagenaar, E.; vanTellingen, O.; de Waart, D.R.; Oude Elferink, R.P.; van de Wetering, K.; Schinkel, A.H. Impact of Abcc2 (Mrp2) and Abcc3 (Mrp3)on the in vivo elimination of methotrexate and its main toxic metabolite 7-hydroxymethotrexate. Clin. Cancer Res., 2008, 14, 8152-8160.
398. Zehnpfennig, B.; Urbatsch, I.L.; Galla, H.J. Functional reconstitution of human ABCC3 into proteoliposomes reveals a transportmechanism with positive cooperativity. Biochemistry, 2009, 48,4423-4430.
399. Leggas, M.; Adachi, M.; Scheffer, G.L.; Sun, D.; Wielinga, P.; Du, G.; Mercer, K.E.; Zhuang, Y.; Panetta, J.C.; Johnston, B.; Scheper, R.J.; Stewart, C.F.; Schuetz, J.D. Mrp4 confers resistance to topotecan and protects the brain from chemotherapy. Mol. Cell. Biol.,2004, 24, 7612-7621.
400. Tian, Q.; Zhang, J.; Tan, T.M.; Chan, E.; Duan, W.; Chan, S.Y.; Boelsterli, U.A.; Ho, P.C.; Yang, H.; Bian, J.S.; Huang, M.; Zhu, Y.Z.; Xiong, W.; Li, X.; Zhou, S. Human multidrug resistance associated protein 4 confers resistance to camptothecins. Pharm. Res., 2005, 22, 1837-1853.
401. Chen, Z.S.; Lee, K.; Walther, S.; Raftogianis, R.B.; Kuwano, M.; Zeng, H.; Kruh, G.D. Analysis of methotrexate and folate transportby multidrug resistance protein 4 (ABCC4): MRP4 is a componentof the methotrexate efflux system. Cancer Res., 2002, 62, 3144-3150.
402. Wijnholds, J.; Mol, C.A.; van Deemter, L.; de Haas, M.; Scheffer, G.L.; Baas, F.; Beijnen, J.H.; Scheper, R.J.; Hatse, S.; De Clercq, E.; Balzarini, J.; Borst, P. Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc. Natl. Acad. Sci. U. S. A., 2000, 97, 7476-7481.
403. McAleer, M.A.; Breen, M.A.; White, N.L.; Matthews, N. pABC11(also known as MOAT-C and MRP5), a member of the ABC family of proteins, has anion transporter activity but does not confermultidrug resistance when overexpressed in human embryonic kidney 293 cells. J. Biol. Chem., 1999, 274, 23541-23548.
404. Belinsky, M.G.; Chen, Z.S.; Shchaveleva, I.; Zeng, H.; Kruh, G.D. Characterization of the drug resistance and transport properties ofmultidrug resistance protein 6 (MRP6, ABCC6). Cancer Res.,2002, 62, 6172-6177.
405. Chen, Z.S.; Hopper-Borge, E.; Belinsky, M.G.; Shchaveleva, I.; Kotova, E.; Kruh, G.D. Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol. Pharmacol., 2003, 63, 351-358.
406. Guo, Y.; Kotova, E.; Chen, Z.S.; Lee, K.; Hopper-Borge, E.; Belin-sky, M.G.; Kruh, G.D. MRP8, ATP-binding cassette C11(ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonylmethoxyethyl)adenine. J. Biol. Chem., 2003, 278,29509-29514.
407. Ono, N.; Van der Heijden, I.; Scheffer, G.L.; Van de Wetering, K.; Van Deemter, E.; De Haas, M.; Boerke, A.; Gadella, B.M.; DeRooij, D.G.; Neefjes, J.J.; Groothuis, T.A.; Oomen, L.; Brocks L.; Ishikawa, T.; Borst, P. Multidrug resistance-associated protein 9(ABCC12) is present in mouse and boar sperm. Biochem. J., 2007,406, 31-40.
408. Nozaki, Y.; Kusuhara, H.; Kondo, T.; Hasegawa, M.; Shiroyanagi, Y.; Nakazawa, H.; Okano, T.; Sugiyama, Y. Characterization of theuptake of organic anion transporter (OAT) 1 and OAT3 substratesby human kidney slices. J. Pharmacol. Exp. Ther., 2007, 321, 362-369.
409. Takeda, M.; Khamdang, S.; Narikawa, S.; Kimura, H.; Hosoya-mada, M.; Cha, S.H.; Sekine, T.; Endou, H. Characterization ofmethotrexate transport and its drug interactions with human organicanion transporters. J. Pharmacol. Exp. Ther., 2002, 302, 666-671.
410. Burckhardt, B.C.; Burckhardt, G. Transport of organic anionsacross the basolateral membrane of proximal tubule cells. Rev.Physiol. Biochem. Pharmacol., 2003, 146, 95-158.
411. Badagnani, I.; Castro, R.A.; Taylor, T.R.; Brett, C.M.; Huang, C.C.; Stryke, D.; Kawamoto, M.; Johns, S.J.; Ferrin, T.E.; Carlson, E.J.; Burchard, E.G.; Giacomini, K.M. Interaction of methotrexatewith organicanion transporting polypeptide 1A2 and its geneticvariants. J. Pharmacol. Exp. Ther., 2006, 318, 521-529.
412. Nozawa, T.; Minami, H.; Sugiura, S.; Tsuji, A.; Tamai, I. Role oforganic anion transporter OATP1B1 (OATP-C) in hepatic uptakeof irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleo-tide polymorphisms. Drug Metab. Dispos., 2005, 33, 434-439.
413. Konig, J.; Seithel, A.; Gradhand, U.; Fromm, M.F. Pharmacoge-nomics of human OATP transporters. Naunyn Schmiedebergs Arch. Pharmacol., 2006, 372, 432-443.
414. van de Steeg, E.; van der Kruijssen, C.M.; Wagenaar, E.; Burggraaff, J.E.; Mesman, E.; Kenworthy, K.E.; Schinkel, A.H. Methotrexate pharmacokinetics in transgenic mice with liver-specific expression of human organic anion-transporting polypeptide 1B1 (SLCO1B1). Drug Metab. Dispos., 2009, 37, 277-281.
415. Nozawa, T.; Imai, K.; Nezu, J.; Tsuji, A.; Tamai, I. Functionalcharacterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J. Pharmacol. Exp. Ther., 2004, 308,438-445.
416. Mikkaichi, T.; Suzuki, T.; Onogawa, T.; Tanemoto, M.; Mizutamari, H.; Okada, M.; Chaki, T.; Masuda, S.; Tokui, T.; Eto, N.; Abe, M.; Satoh, F.; Unno, M.; Hishinuma, T.; Inui, K.; Ito, S.; Goto, J.; Abe, T. Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc. Natl.Acad. Sci. U. S. A., 2004, 101, 3569-3574.
417. Laing, N.M.; Belinsky, M.G.; Kruh, G.D.; Bell, D.W.; Boyd, J.T.; Barone, L.; Testa, J.R.; Tew, K.D. Amplification of the ATP-binding cassette 2 transporter gene is functionally linked with en-hanced efflux of estramustine in ovarian carcinoma cells. Cancer Res., 1998, 58, 1332-1337.
418. Childs, S.; Yeh, R.L.; Hui, D.; Ling, V. Taxol resistance mediatedby transfection of the liver-specific sister gene of P-glycoprotein. Cancer Res., 1998, 58, 4160-4167.
419. Lovejoy, K.S.; Todd, R.C.; Zhang, S.; McCormick, M.S.; D'Aquino, J.A.; Reardon, J.T.; Sancar, A.; Giacomini, K.M.; Lippard, S.J. cis-Diammine(pyridine)chloroplatinum(II), a monofunc-tional platinum(II) antitumor agent: uptake, structure, function, andprospects. Proc. Natl. Acad. Sci. U. S. A., 2008, 105, 8902-8907.
420. Zhang, S.; Lovejoy, K.S.; Shima, J.E.; Lagpacan, L.L.; Shu, Y.; Lapuk, A.; Chen, Y.; Komori, T.; Gray, J.W.; Chen, X.; Lippard., S J.; Giacomini K.M. Organic cation transporters are determinantsof oxaliplatin cytotoxicity. Cancer Res., 2006, 66, 8847-8857.
421. Yonezawa, A.; Masuda, S.; Yokoo, S.; Katsura, T.; Inui, K. Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 andmultidrug and toxin extrusion family). J. Pharmacol. Exp. Ther.,2006, 319, 879-886.
422. Okabe, M.; Szakacs, G.; Reimers, M.A.; Suzuki, T.; Hall, M.D.; Abe, T.; Weinstein, J.N.; Gottesman, M.M. Profiling SLCO andSLC22 genes in the NCI-60 cancer cell lines to identify drug uptaketransporters. Mol. Cancer Ther., 2008, 7, 3081-3091.
423. Lu, X.; Gong, S.; Monks, A.; Zaharevitz, D.; Moscow, J.A. Correlation of nucleoside and nucleobase transporter gene expressionwith antimetabolite drug cytotoxicity. J. Exp. Ther. Oncol., 2002,2, 200-212.
424. Huang, Y.; Anderle, P.; Bussey, K.J.; Barbacioru, C.; Shankavaram, U.; Dai, Z.; Reinhold, W.C.; Papp, A.; Weinstein, J.N.; Sadee, W. Membrane transporters and channels: role of thetransportome in cancer chemosensitivity and chemoresistance. Cancer Res., 2004, 64, 4294-4301.
425. Griffiths, M.; Beaumont, N.; Yao, S.Y.; Sundaram, M.; Boumah, C.E.; Davies, A.; Kwong, F.Y.; Coe, I.; Cass, C.E.; Young, J.D.; Baldwin, S.A. Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeuticdrugs. Nat. Med., 1997, 3, 89-93.
426. Gati, W.P.; Paterson, A.R.; Larratt, L.M.; Turner, A.R.; Belch, A.R. Sensitivity of acute leukemia cells to cytarabine is a correlateof cellular es nucleoside transporter site content measured by flowcytometry with SAENTA-fluorescein. Blood, 1997, 90, 346-353.
427. Nagai, K.; Nagasawa, K.; Kihara, Y.; Okuda, H.; Fujimoto, S. Anticancer nucleobase analogues 6-mercaptopurine and 6-thioguanine are novel substrates for equilibrative nucleoside transporter 2. Int. J. Pharm., 2007, 333, 56-61.
428. Mackey, J.R.; Yao, S.Y.; Smith, K.M.; Karpinski, E.; Baldwin, S.A.; Cass, C.E.; Young, J.D. Gemcitabine transport in xenopusoocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J. Natl. Cancer Inst., 1999, 91, 1876-1881.
429. +-dependent nucleoside transporters. Pharm. Res., 1997, 14,1524-1532.
430. Mackey, J.R.; Baldwin, S.A.; Young, J.D.; Cass, C.E. Nucleosidetransport and its significance for anticancer drug resistance. Drug Resist. Updat., 1998, 1, 310-324.
431. Lostao, M.P.; Mata, J.F.; Larrayoz, I.M.; Inzillo, S.M.; Casado, F.J.; Pastor-Anglada, M. Electrogenic uptake of nucleosides andnucleoside-derived drugs by the human nucleoside transporter 1(hCNT1) expressed in Xenopus laevis oocytes. FEBS Lett., 2000,481, 137-140.
432. +-dependent purine nucleoside trans-porter from human kidney: cloning and functional characterization. Am. J. Physiol., 1997, 273, F1058-1065.
433. +-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidinenucleosides (system cib). J. Biol. Chem., 2001, 276, 2914-2927.
434. Griffith, D.A.; Jarvis, S.M. Nucleoside and nucleobase transportsystems of mammalian cells. Biochim. Biophys. Acta, 1996, 1286,153-181.
435. Hogue, D.L.; Ling, V. A human nucleobase transporter-like cDNA(SLC23A1): member of a transporter family conserved from bacteria to mammals. Genomics, 1999, 59, 18-23.
436. 0,+) reveals the poten-tial of the transporter as a drug target for cancer chemotherapy. Biochem. J., 2008, 414, 343-355.
437. Awasthi, S.; Singhal, S.S.; Srivastava, S.K.; Zimniak, P.; Bajpai, K.K.; Saxena, M.; Sharma, R.; Ziller, S.A., 3rd; Frenkel, E.P.; Singh, S.V.; et al. Adenosine triphosphate-dependent transport ofdoxorubicin, daunomycin, and vinblastine in human tissues by amechanism distinct from the P-glycoprotein. J. Clin. Invest., 1994,93, 958-965.
438. Vulevic, B.; Chen, Z.; Boyd, J.T.; Davis, W., Jr.; Walsh, E.S.; Belinsky, M.G.; Tew, K.D. Cloning and characterization of humanadenosine 5'-triphosphate-binding cassette, sub-family A, trans-porter 2 (ABCA2). Cancer Res., 2001, 61, 3339-3347.
439. Boonstra, R.; Timmer-Bosscha, H.; van Echten-Arends, J.; van der Kolk, D.M.; van den Berg, A.; de Jong, B.; Tew, K.D.; Poppema,S.; de Vries, E.G. Mitoxantrone resistance in a small cell lung can-cer cell line is associated with ABCA2 upregulation. Br. J. Cancer,2004, 90, 2411-2417.