P-glycoprotein-mediated efflux as a major factor in the variance of absorption and distribution of drugs: Modulation of chemotherapy resistance

Methods and Findings in Experimental and Clinical Pharmacology

Volumn 24, Issue 8, 2002, Pages 501-514

  Johnson, William W ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; ANTINEOPLASTIC AGENT; CYTOCHROME P450 3A4; DNA; GLYCOPROTEIN P; MESSENGER RNA; MULTIDRUG RESISTANCE PROTEIN 1; VALSPODAR; XENOBIOTIC AGENT;

ACTIVE TRANSPORT; AREA UNDER THE CURVE; ARTICLE; BLOOD BRAIN BARRIER; CANCER CELL; CANCER CHEMOTHERAPY; DNA POLYMORPHISM; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG TRANSPORT; HUMAN; INTESTINE ABSORPTION; LIPID BILAYER; MULTIDRUG RESISTANCE; NEUROTOXICITY; NONHUMAN; PLACENTA; PROGNOSIS; TERATOGENICITY; TISSUE DISTRIBUTION;

ABSORPTION; ADJUVANTS, PHARMACEUTIC; ANIMALS; ANTINEOPLASTIC AGENTS; CHEMOTHERAPY, ADJUVANT; DRUG RESISTANCE, MULTIPLE; DRUG RESISTANCE, NEOPLASM; HUMANS; P-GLYCOPROTEIN; TISSUE DISTRIBUTION;

EID: 0036815092     PISSN: 03790355     EISSN: None     Source Type: Journal    
DOI: 10.1358/mf.2002.24.8.705071     Document Type: Article

References (118)

1. Gottesman, M.M., Pastan. I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 1993, 62: 385-427.
2. Gottesman, M.M., Pastan, I. Biochemistry of multidrug resistance mediated by the multidrug transporter: Annu Rev Biochem 1993, 62: 385-427.
3. Gottesman, M.M., Pastan, I., Ambudkar S.V. P-glycoprotein and muultidrug resistance. Curr Opin Genet Dev 1996, 6: 610-17.
4. Fisher, G.A., Lum, B.L., Hausdorff, J., Sikic, B.I. Pharmacological considerations in the modulation of multidrug resistance. Eur J Cancer 1996 32(6): 1082-8.
5. Siegsmund, M.J., Cardarelli, C., Aksentijevich, I., Sugimoto, Y., Pastan, I., Gottesman, M.M. Ketoconazole effectively reverses multidrug resistance in highly resistant KB Cells. J Urol 1994. 151: 485-91.
6. Wang, E.-J., Lew, K., Barecki, M.E., Casciano, C.N., Clement, R.P., Johnson, W.W. Quantitative distinctions of active site molecular recognition by P-glycoprotein and cytochrome P450 3A4. Chemical Res Tox 2001, 14(12): 1596-603.
7. Monahan, B.P., Ferguson, C.L., Killeavy, E.S., Lloyd, B.K., Troy, J., Cantilena, L.R. Torsades de Pointes Occurring in association. with terfenadine rise, JAMA 1990, 264(21): 2788-90.
8. Neuvonen, P.J., Kantola, T., Kivisto, K.T. Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 1998, 63(3): 332-41.
9. Ambudkar, S.V., Dey, S., Hrycyna, C.A., Ramachandra, M., Pastan, I., Gottesman, M.M. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol 1999, 39: 361-98.
10. Brinkmann, U., Eichelbaum, M, Polymorphisms in the ABC drug transporter gene MDRI. Pharmacogenomics J 2001, 1(1): 59-64.
11. Kerb, R., Hoffmeyer, S., Brinkmann, U. ABC drug transporters: Hereditary polymorphisms and pharmacological impact in MDRI, MRP1 and MRP2. Pharmacogenomics 2001, 2(1): 51-64.
12. Hoffmeyer, S., Burk, O., von Richter, O. et al. Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 2000, 97: 3473-8.
13. Eytan, G.D., Regev, R., Assaraf, Y.G. Functional reconstitution of P-glycoprotein reveals an apparent near stoichiometric drug transport to ATP hydrolysis. J Biol Chem 1996, 271: 3172-8.
14. Ambudkar, S.V., Cardarelli, C.O., Pashinsky, E., Stein, W.D. Relation between the turnover number for vinblastine transport and for vinblastine-stimulated ATP hydrolysis by human P-glycoprotein. J Biol Chem 1997, 272: 21160-6.
15. Stein, W.D. Kinetics of the multidrug transporter (P-glycoprotein) and its reversal. Physiol Rev 1997, 77: 545-90.
16. Shapiro, A.B., Ling, V. Stoichiometry of coupling of rhodamine 123 transport to ATP hydrolysis by P-glycoprotein Eur J Biochem 1998, 254: 189-93.
17. Wang, E.-J., Casciano, C.N., Clement, R.P., Johnson, W.W. Two transport binding sites of P-glycoprotein are unequal yet contingent: Initial rate kinetic analysis by ATP hydrolysis demonstrates intersite dependency. Biochim Biophys Acta 2000, 1481, 63-74.
18. Sauna, Z.E, Ambudkar, S.V. Evidence for a requirement for ATP hydrolysis at two distinct steps during a single turnover of the catalytic cycle of human P-glycoprotein. Proc Nat Acad Sci USA 2000, 97: 2515-20.
19. Sauna, Z.E., Ambudkar, S.V. Characterization of the catalytic cycle of ATP hydrolysis by human P-glycoprotein: The two ATP hydrolysis events in a single catalytic cycle are kinetically similar but affect different functional outcomes. J Biol Chem 2001, 276: 11653-61.
20. Senior, A.E., Bhagat, S. P-glycoprotein shows strong catalytic cooperatively between the two nucleotide sites. Biochemistry 1998, 37: 831-56.
21. Shapiro, AB., Ling, V. Extraction of Hoechst 33342 from the cytoplasmic leaflet of the plasma membrane by P-glycoprotein. Eur J Biochem 1997, 250: 122-9.
22. Dey, S., Ramachandra, M., Pasture I., Gottesman, M.M. Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein. Proc Nat Acad Sci USA 1997, 94: 10594-9.
23. Sharom, F.J., Liu, R., Qu, Q., Romsicki. Y. Exploring the structure and function of the P-glycoprotein multidrug transporter using fluorescence spectroscopic tools. Semin Cell Dev Biol 2001, 12(3): 257-65.
24. Shapiro, A.B., Ling, V. Positively cooperative sites for drug transport by P-glycoprotein with distinct drug specificities. Eur J Biochem 1997, 250: 130-7.
25. Wang, E.-J., Casciano, C.N., Clement, R.P., Johnson, W.W. Cooperativity in the inhibition qf P-glycoprotein-mediated daunorubicin transport: Evidence for half-of-the-sites reactivity. Arch Biochem Biophys 2000, 383(1): 91-8.
26. Wang, G., Pincheira, R., Zhang, J.-T. Dissection of drug-binding-induced conformational changes in P-glycoprotein. Eur J Biochem 1998, 255: 383-90.
27. Pascaud, C., Garrigos, M., Orlowski, S. Multidrug resistance transporter P-glycoprotein has distinct but interacting binding sites for cytotoxic drugs and reversing agents. Biochem J 1998, 333: 351-8.
28. Hrycyna, C.A., Ramachandra, M., Ambudkar, S.V. et al. Mechanism of action of human P-glycoprotein ATPase activity, Photochemical cleavage during a catalytic transition state using orthovanadate reveals cross-talk between the two ATP sites. J Biol Chem 1998, 273: 16631-4.
29. Loo, T.W., Clarke, D.M. Covalent modification of human P-glycoprotein mutants containing a single cysteine in either nucleotide-binding fold abolishes drag-stimulated ATPase activity. J Biol Chem 1995, 270: 22957-61.
30. Wang, E.J., Casciano, C.N., Clement, R.P., Johnson, W.W. Active transport of fluorescent P-glycoprotein substrates: Evaluation as markers and interaction with inhibitors Biochem Biophys Res Commun 2001, 289(2): 580-5.
31. Schinkel, A.H., Smit, J.J., van Tellingen, O. et al. Disruption of the mouse mdrla P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994, 77(4): 491-502.
32. Schinkel, A.H., Mayer, U., Wagenaar, E. et al. Normal viability and altered pharmacokinetics in mice lacking mdrI-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci USA 1997, 94(8): 4028-33.
33. Mayer, U., Wagenaar, E., Dorobek, B., Beijnen, J.H., Borst, P., Schinkel, A.H. Full blockade of intestinal P-glycoprotein and extensive inhibition of blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833. J Clin Invest 1997, 100(10): 243O-6.
34. Fricker, G., Drewe. J., Huwyler, J., Gutmann, H., Beglinger, C. Relevance of p-glycoprotein for the enteral absorption of cyclosporin A: In vitro-in vivo correlation. Br J Pharmacol 1996, 118(7): 1841-7.
35. Gonzalez, O., Colombo, T., De Fusco, M., Imperatori, L., Zucchetti, M., D'Incalci, M. Changes in doxorubicin distribution and toxicity in mice pretreated with the cyclosporin analogue SDZ PSC 833. Cancer Chemother Pharmacol 1995, 36(4): 335-40.
36. van Asperen, J., van Tellingen, O., van der Valk, M.A., Rozenhart, M., Beijnen, J.H. Enhanced oral absorption and decreased elimination of paclitaxel in mice cotreated with cyclosporin A. Clin Cancer Res 1998, 4(10): 2293-7.
37. Lankas, G.R., Cartwright, M.E., Umbenhauer, D. P-glycoprotein deficiency in a subpopulation of CF-I mice enhances avermectin-induced neurotoxicity. Toxicol Appl Pharmacol 1997, 143(2): 357-65.
38. de Lannoy, I.A., Mandin, R.S., Silverman, M. Renal secretion of vinblastine, vincristine and colchicine in vivo. J Pharmacol Exp Ther 1994, 268(1): 388-95.
39. Lum, B.L., Fisher, G.A., Brophy, N.A. et al. Clinical trials of modulation of multidrug resistance. Pharmacokinetic and pharmacodynamic considerations. Cancer 1993, 72 (11 Suppl.): 3502-14.
40. Choo, E.F., Leake, B., Wandel, C. et al. Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-I protease inhibitors into brain and testes. Drug Metab Dispos 2000, 28(6): 655-60.
41. Savolainen, J., Edwards, J.E., Morgan, M.E., McNamara, P.J., Anderson, B,D. Effects of a p-glycoprotein inhibitor on brain and plasma concentrations of anti-human immunodeficiency virus drugs administered in combination in rats. Drug Metab Dispos 2002, 30(5): 479-82.
42. Westphal, K., Weinbrenner, A., Zschiesche, M. et al. Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: A new type of drug/drug interaction. Clin Pharmacol Ther 2000, 68(4): 345-55.
43. Greiner, B., Eichelbaum, M., Fritz, P. et al. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J Clin Invest 1999, 104(2): 147-53.
44. Abolhoda, A., Wilson, A.E., Ross, H., Danenberg, P.V., Burt, M., Scotto, K.W. Rapid activation of MDRI gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin. Clin Cancer Res 1999, 5(11): 3352-6.
45. Ayrton, A., Morgan, P. Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica 2001, 31(8-9): 469-97.
46. Kim, R.B. Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab Rev 2002, 34(1-2): 47-54.
47. Drescher, S., Schaeffeler, E., Hitzl, M. et al. MDRI gene polymorphisms and disposition of the P-glycoprotein substrate fexofenadine. Br J Clin Pharmacol 2002, 53(5): 526-34.
48. Schaeffeler, E., Eichelbaum, M., Brinkmann, U. et al. Frequency of C3435T polymorphism of MDRI gene in African people. Lancet 2001, 358(9279): 383-4.
49. Ameyaw, M.M., Regateiro, F., Li, T. et al. MDRI pharmacogenetics: Frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics 2001, 11(3): 217-21.
50. Fellay, J., Marzolini, C., Meaden, E.R. et al. The Swiss HIV Cohort Study. Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter I: A pharmacogenetics study. Lancet 2002, 359(9300): 30-6.
51. Kim, R.B., Leake, B.F., Choo, E.F. et al. Identification of functionally variant MDRI alleles among Earopean Americans and African Americans. Clin Pharmacol Ther 2001, 70(2): 189-99.
52. Schuetz, E.G., Furuya, K.N., Schuetz, LD. Interindividual variation in expression of P-glycoprotein in normal human liver and secondary hepatic neoplasms. J Pharmacol Exp Ther 1995 275(2): 1011-8.
53. Fontana, R.J., Lown, K.S., Paine, M.F. et al. Effects of a chargrilled meat diet on expression of CYP3A, CYPIA, and P-glycoprotein levels in healthy volunteers. Gastroenterology 1999, 117(1): 89-98.
54. Masuda, S., Uemoto, S., Hashida, T., Inomata, Y., Tanaka, K., Inui, K. Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient. Clin Pharmacol Ther 2000 68(1): 98-103.
55. Potocnik, U., Glavac, M.R., Golouh, R., Glavac, D. The role of P-glycoprotein (MDRI) polymorphisms and mutations in colorectal cancer. Pflugers Arch 2001, 442 (6 Suppl. 1): R182-3.
56. Rund, D., Azar, I., Shperling, O. A mutation in the promoter of the multidrug resistance gene (MDRI) in human hematological malignancies may contribute to the pathogenesis of resistant disease. Adv Exp Med Biol 1999, 457: 71-5.
57. Dhooge, C., De Moerloose, B., Laureys, G. et al. Expression of the multidrug transporter P-glycoprotein is highly correlated with clinical outcome in childhood acute lymphoblastic leukemia: Results of a long-term prospective study. Leuk Lymphoma 2002, 43(2): 309-14.
58. Tada, Y., Wada, M., Kuroiwa, K. et al. MDRI gene overexpression and altered degree qf methylation at the promoter region in bladder cancer daring chemotherapeutic treatment. Clin Cancer Res 2000 6(12): 4618-27.
59. Borst, P., Evers, R., Kool, M., Wijnholds, J. A family of drug transporters: The multidrug resistance-associated proteins. J Natl Cancer Inst 2000 92(16): 1295-302.
60. Kruh, G.D., Zeng, H., Rea, P.A. et al. MRP subfamily transporters and resistance to anticancer agents. J Bioenerg Biomembr 2001, 33(6): 493-501.
61. Suzuki, T., Nishio, K., Tanabe, S. The MRP family and anticancer drug metabolism. Curr Drug Metab 2001, 2(4): 367-77.
62. Wang, E.-J., Casciano, C.N., Clement, R. P., Johnson, W.W. Inhibition of P-glycoprotein transport function by grapefruit juice psoralen. Pharm Res 2001, 18(4): 432-8.
63. Wang, E.-J., Lew, K., Casciano, C.N., Clement, R.P., Johnson, W.W. Characterization of common azole antifungals contrasted for interaction with P-glycoprotein. Antimicrob Agents Chemother 2002, 46(1): 160-5.
64. Wang, E.-J., Cascano, C.N., Clement, R.P., Johnson, W.W. HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors ofP-glycoprotein. Pharm Res 2001, 18(6): 800-6.
65. Wang, E., Casciano, C.N., Clement, R.P., Johnson, W.W. Thefarnesyl protein transferase inhibitor SCH66336 is a potent inhibitor of MDRI product P-glycoprotein. Cancer Res 2001, 61(20): 7525-9.
66. Yamazaki, M., Neway, W.E., Ohe, T. et al. In vitro substrate identification studies for p-glycoprotein-mediated transport. Species difference and predictability of in vivo results. J Pharmacol Exp Ther 2001, 296(3): 723-35.
67. Annaert, P.P., Turncliff, R.Z., Booth, C.L., Thakker, D.R., Brouwer, K.L. P-glycoprotein-mediated in vitro biliary, excretion in sandwich-cultured rat hepatocytes. Drug Metab Dispos 2001 29(10): 1277-83.
68. Megard, I., Garrigues. A., Orlowski, S., Jorajuria, S., Clayette, P., Ezan, E, Mabondzo A. A co-culture-based model of human blood-brain barrier: Application to active transport of indinavir and in vivo-in vitro correlation. Brain Res 2002 927(2): 153-67.
69. Adachi, Y., Suzuki, H., Sugiyama, Y. Comparative studies on in vitro methods for evaluating in vivo function of MDRI P-glycoprotein. Pharm Res 2001, 18(12): 1660-8.
70. Chiou, W.L., Chung, S.M., Wu, T.C., Ma, C. A comprehensive account on the role of efflux transporters in the gastrointestinal absorption of 13 commonly used substrate drugs in humans. Int J Clin Pharmacol Ther 2001, 39(3): 93-101.
71. Taipalensuu, J., Tornblom, H., Lindberg, G. et al. Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers. J Pharmacol Exp Ther 2001, 299(1): 164-70.
72. Gottesman, M.M., Fojo, T., Bates, S.E. Multidrug resistance in cancer: Role of ATP-dependent transporters. Nature Rev Cancer 2002, 2(1): 48-58.
73. Fojo, A.T., Ueda, K., Slamon, D.J., Poplack, D.G., Gottesman, M.M., Pastan. I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci USA 1987, 84(1): 265-9.
74. Leith, C.P., Kopecky, K.J, Chen, I,M. Frequency and clinical significance of the expression of the multidrug resistance proteins MDRI/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: A Southwest Ontology Group Study, Blood 1999, 94(3): 1086-99.
75. Trock, B.J., Leonessa, F., Clarke, R. Multidrug resistance in breast cancer: A meta-analysis of MDRI/gp170 expression and its possible functional significance. J Natl Cancer Inst 1997, 89(13): 917-31.
76. Mechetner, E., Kyshtoobayeva, A., Zonis, S. et al. Levels of multidrug resistance (MDRI) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. Clin Cancer Res 1998, 4(2): 389-98.
77. Baekelandt, M.M., Holm, R., Nesland, J.M., Trope, C.G., Kristensen, G.B. P-glycoprotein expression is a marker for chemotherapy resistance and prognosis in advanced ovarian cancer. Anticancer Res 2000, 20(2B): 1061-7.
78. Ciarmiello, A., Del Vecchio, S., Silvestro, P. et al. Tumor clearance of technetium 99m-sestamibi as a predictor of response to neoadjuvant chemotherapy for locally advanced breast cancer. J Clin Oncol 1998, 16(5): 1677-83.
79. Yu, D., Liu, B., Jing, T, et al. Overexpression of both p185c-erbB2 and p170mdr-1 renders breast cancer cells highly resistant to taxol. Oncogene 1998, 16(16): 2087-94.
80. Tsuro, T., Lida, H., Tsukagoshi, S., Sakurai, Y. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 1981, 41(5): 1967-72.
81. Twentyman, P.R., Bleehen, N.M. Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporin. Eur J Cancer 1991, 27(12): 1639-42.
82. List, A.F., Spier, C., Greer, J. al. Phase 1/11 trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia. J Clin Oncol 1993, 11(9): 1652-60.
83. Aszalos, A., Ross, D.D. Biochemical and clinical aspects of efflux pump related resistance to anti-cancer drugs. Anticancer Res 1998, 18(4C): 2937-44.
84. Liu, M., Bryant, M.S., Chen, J. et al. Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res 1998, 58(21): 4947-56.
85. Nielsen, L.L., Shi, B., Hajian, G, et al. Combination therapy with the farnesyl protein transferase inhibitor SCH66336 and SCH58500 (p53 adenovirus) in preclinical cancer models. Cancer Res 1999, 59(23): 5896-901.
86. Shi, B., Yaremko, B., Hajian,. G. et al. The farnesyl protein transferase inhibitor SCH66336 synergizes with taxanes in vitro and enhances their antitumor activity in vivo. Cancer Chemother Pharmacol 2000, 46(5): 387-93.
87. Ford, J.M. Experimental reversal of P-glycoprotein-mediated multidrug resistance by pharmacological chemosensitisers. Eur J Cancer 1996, 32A(6): 991-1001.
88. Sonneveld, P., Wiemer. E. Inhibitors of multidrug resistance. Curr Opin Oncol 1997, 9(6): 543-8.
89. Germann, U.A., Shlyakhter, D., Mason, V.S. et al. Cellular and biochemical characterization of VX-710 ns a chemosensitizer: Reversal of P-glycoprotein-mediated multidrug resistance in vitro. Anticancer Drugs 1997, 8(2): 125-40.
90. Malkhandi, P.J., Ferry, D.R., Boer, R., Kerr, D.J. P-Glycoprotein has a drug acceptor site for 1, 4-dihydropyridines which is localised on an intracellular domain. Proc Am Assoc Cancer Res 1995, 36: Abst 1977.
91. Safa, A.R. et al. The relationship between modulation of multidrug resistance by novel, potent agents and their affinities for P-glycoprotein. 9th NCI-EORTC Symp New Drugs Cancer Ther (Mar 12-Mar 15, Amsterdam) 1996, Abst 419.
92. Boer, R. et al. Interaction of cytostatics and chemosensitizers with the dexniguldipine binding site on P-glycoprotein. Proc Am Assoc Cancer Res 1995, 36: Abst 1973.
93. Martin, C., Berridge, G., Mistry, P., Higgins, C., Charlton, P., Callaghan, R. The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein. Br J Pharmacol 1999, 128(2): 403-11.
94. Mistry, P., Stewart, A.J., Dangerfield, W. et al. In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576. Cancer Res 2001, 61(2): 749-58.
95. van Zuylen, L., Sparreboom, A., van der Gaast, A. et al. Disposition of docetaxel in the presence of P-glycoprotein inhibition by intravenous administration of R101933. Eur J Cancer 2002, 38(8): 1090-9.
96. Wouters, W., Janssens, F., van Dun, J., Krekels, M., Smets, G. R101933 is an antagonist of Pgp and modulates resistance to different chemotherapy agents. Proc Am Assoc Cancer Res 1999, 40: Abst 4374.
97. Kimura, Y., Aoki, J., Kohno, M., Ooka, H., Tsuruo, T., Nakanishi, O. P-glycoprotein inhibition by the multidrug resistance-reversing agent MS-209 enhances bioavailability and antitumor efficacy of orally administered paclitaxel. Cancer Chemother Pharmacol 2002, 49(4): 322-8.
98. Dixon, R., Toyonaga, B. P-glycoprotein inhibitor OC144-093: Phase 1 intravenous and oral pharmacokinetics of a novel multidrug resistance modulator. Proc Am Assoc Cancer Res 2000, 41: Abst 3863.
99. Leonessa, F., Kim, J.H., Ghiorghis, A. et al. C-7 analogues of progesterone as potent inhibitors of the P-glycoprotein efflux pump. J Med Chem 2002, 45(2): 390-8.
100. Roe, M. et al. Reversal of P-glycoprotein mediated multidrug resistance by novel anthranilamide derivatives. Bioorg Med Chem Lett 1999, 9(4): 595-600.
101. Germann, U.A., Shlyakhter, D., Mason, V.S., Ford, P.J., Harding, M.W. VX-853: A novel bispecific chemosensitizer which reverses P-glycoprotein- and MRP-mediated multidrug resistance. Proc Am Assoc Cancer Res 1996, 37: Abst 2283.
102. Kusunoki, N., Takara, K., Tanigawara, Y. et al. Inhibitory effects of a cyclosporin derivative, SDZ PSC 833, on transport of doxorubicin and vinblastine via human P-glycoprotein Jpn J Cancer Res 1998, 89(11): 1220-8.
103. Reddy, V.R., Buben, J.A., Truex, L.L. et al. The toxicity and pharmacokinetic interaction of LY335979, an inhibitor of P-glycoprotein, with doxorubicin in beagle dogs. Proc Am Assoc Cancer Res 1998, 39: Abst 511.
104. Dantzig, A.H., Shepard, R.L., Cao, J. et al. Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropy-Idibenzosuberane modulator, LY335979. Cancer Res 1996, 56(18): 4171-9.
105. Tiberghien, F., Wenandy T., Loor, F. The potent immunosuppressive cyclosporin FR901459 inhibits the human P-glycoprotein and formyl peptide receptor fuctions. J Antibiot 2000, 53(5): 509-15.
106. Wang, E.J., Lew, K., Casciano, C.N., Clement, R.P., Johnson, W.W. Interaction of common azole antifungals with P glycoprotein. Antimicrob Agents Chemother 2002, 46(1): 160-5.
107. Martin, C., Berridge, G., Higgins, C.F., Callaghan, R. The multi-drug resistance reversal agent SR33557 and modulation of vinca alkaloid binding to P-glycoprotein by an allosteric interaction. Br J Pharmacol 1997, 122(4): 765-71.
108. Maitrejean, M., Comte, G., Barron, D., El Kirat, K., Conseil, G., Di Pietro, A. The flavanolignan silybin and its hemisynthetic derivatives, a novel series of potential modulators of P-glycoprotein. Bioorg Med Chem Lett 2000, 10(2): 157-60.
109. Pfister, J.R. et al. Methanodibettaosuberylpiperazines as potent multidrug resistance reversal agents. Bioorg Med Chem Lett 1995, 5(21): 2473.
110. Traunecker, H.C., Stevens, M.C., Kerr, D.J., Ferry, D.R. The acridonecarboramide GF120918 potently reverses P-glycoprotein-mediated resistance in human sarcoma MES-Dx5 cells. Br J Cancer 1999, 81(6): 942-51.
111. Stupp, R., Bauer, J., Pagani, O. et al. Ventricular arrhythmia and torsade de pointe: Dose limiting toxicities of the MDR-modulator S9788 in a phase I trial. Ann Oncol 1998 9(11): 1233-42.
112. Fields, A., Hochster, H., Runowicz, C. et al. PSC833: Initial clinical results in refractory ovarian cancer patients. Curr Opin Oncol 1998, 10 (Suppl 1): S21.
113. Hyafil, F., Vergely, C., Du Vignaud, P., Grand-Perret, T. In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Res 1993, 53(19): 4595-602.
114. Dantzig, AH., Law. K.L., Cao, J, Starling, J.J. Reversal multidrug resistance by the P-glycoprotein modulator, LY335979, from the bench front to the clinic. Curr Med Chem 2001 8(1): 39-50.
115. Toppmeyer, D., Seidman, A.D., Pollak, M. et al, Safety and efficacy of the multidrug resistance inhibitor Incel (biricodar: VX-710) ia combination with paclitaxel for advanced breast cancer refractory to paclitaxel. Clin Cancer Res 2002 8(3): 670-8.
116. Sonneveld, P, Reversal of multidrug resistance in acute myeloid leukaemia and other haematological malignancies Eur J Cancer 1996, 32A(6)): 1062-9.
117. Ross, D.D., Doyle, L.A., Schiffer, C.A., et al. Expression multidrug resistance-associated protein (MRP) mRNA in blast cells from acute myeloid leukemia (AML) patients. Leukemia 1996 10(1): 48-55.
118. Dietrich, C.G., de Waart, D.R., Ottenhoff, R., Schoots, I.G., Elferink, R.P, Increased bioavaitability of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-blpyridine in MRP2-deficient rats. Mol Pharmacol 2001, 59(5): 974-80.