New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I

Current Drug Metabolism

Volumn 10, Issue 10, 2009, Pages 1075-1126

  Mo, Sui Lin ^a,b   Zhou, Zhi Wei ^b   Yang, Li Ping ^c   Wei, Ming Qian ^d   Zhou, Shu Feng ^b  

^a SUN YAT SEN UNIVERSITY   (China)

^b RMIT UNIVERSITY   (Australia)

^c BEIJING HOSPITAL   (China)

^d GRIFFITH UNIVERSITY   (Australia)

Author keywords

CYP2C9; Inhibitor; Modeling; Pharmacophore; Structure activity relationship; Substrate

Indexed keywords

8 CHLORO 1,2,3,4,4A,5,6,10B OCTAHYDRO 4 METHYLBENZO[F]QUINOLIN 3(2H) ONE; ANGIOTENSIN 2 RECEPTOR ANTAGONIST; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; ANTIARRHYTHMIC AGENT; ANTICOAGULANT AGENT; ANTICONVULSIVE AGENT; ANTIDEPRESSANT AGENT; ANTIFUNGAL AGENT; ANTIINFECTIVE AGENT; ANTIINFLAMMATORY AGENT; ANTINEOPLASTIC AGENT; ANTITHROMBOCYTIC AGENT; BENZODIAZEPINE; CALCIUM CHANNEL BLOCKING AGENT; CYCLOOXYGENASE 2 INHIBITOR; CYTOCHROME P450; HYPNOTIC AGENT; IMMUNOMODULATING AGENT; LEPROSTATIC AGENT; LEUKOTRIENE RECEPTOR BLOCKING AGENT; LOOP DIURETIC AGENT; LY 156735; LY 213829; MUSCARINIC RECEPTOR BLOCKING AGENT; NONSTEROID ANTIINFLAMMATORY AGENT; ORAL ANTIDIABETIC AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; RUBOXISTAURIN; SELECTIVE ESTROGEN RECEPTOR MODULATOR; SEROTONIN UPTAKE INHIBITOR; STEROID; SULFONAMIDE; TALAMPANEL; THROMBOXANE RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG; URICOSURIC AGENT; ZOSUQUIDAR; CYP2C9 PROTEIN, HUMAN; CYTOCHROME P450 2C9; DRUG; PROTEIN BINDING; UNSPECIFIC MONOOXYGENASE;

ARTICLE; BINDING AFFINITY; CHROMOSOME 10; DEALKYLATION; DEHYDROGENATION; DEMETHYLATION; DNA POLYMORPHISM; DRUG HYDROXYLATION; DRUG METABOLISM; DRUG OXIDATION; DRUG STRUCTURE; HORMONE METABOLISM; HUMAN; HYDROGEN BOND; HYDROPHOBICITY; IONIZATION; LIVER; LIVER METABOLISM; MOLECULAR INTERACTION; PH; PKA; STEROID METABOLISM; STRUCTURE ACTIVITY RELATION; TREATMENT FAILURE; ANIMAL; CHEMISTRY; ENZYME SPECIFICITY; METABOLISM; PHYSIOLOGY;

ANIMALS; ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 CYP2C9; HUMANS; PHARMACEUTICAL PREPARATIONS; PROTEIN BINDING; SUBSTRATE SPECIFICITY;

EID: 77649141812     PISSN: 13892002     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920009790820129     Document Type: Article

References (385)

1. Williams, P.A.; Cosme, J.; Sridhar, V.; Johnson, E.F.; McRee, D.E. Mammalian microsomal cytochrome P450 monooxygenase: structural adaptations for membrane binding and functional diversity. Mol. Cell, 2000, 5(1), 121-131.
2. Sansen, S.; Yano, J.K.; Reynald, R.L.; Schoch, G.A.; Griffin, K.J.; Stout, C.D.; Johnson, E.F. Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. J. Biol. Chem., 2007, 282(19), 14348-14355.
3. Yano, J.K.; Hsu, M.H.; Griffin, K.J.; Stout, C.D.; Johnson, E.F. Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. Nat. Struct. Mol. Biol., 2005, 12(9), 822-823.
4. Smith, B.D.; Sanders, J.L.; Porubsky, P.R.; Lushington, G.H.; Stout, C.D.; Scott, E.E. Structure of the human lung cytochrome P450 2A13. J. Biol. Chem., 2007, 282(23), 17306-17313.
5. Schoch, G.A.; Yano, J.K.; Wester, M.R.; Griffin, K.J.; Stout, C.D.; Johnson, E.F. Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site. J. Biol. Chem., 2004, 279(10), 9497-9503.
6. Schoch, G.A.; Yano, J.K.; Sansen, S.; Dansette, P.M.; Stout, C.D.; Johnson, E.F. Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid. J. Biol. Chem., 2008, 283(25), 17227-17237.
7. Williams, P.A.; Cosme, J.; Ward, A.; Angove, H.C.; Matak Vinkovic, D.; Jhoti, H. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature, 2003, 424(6947), 464-468.
8. Wester, M.R.; Yano, J.K.; Schoch, G.A.; Yang, C.; Griffin, K.J.; Stout, C.D.; Johnson, E.F. The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0-Å resolution. J. Biol. Chem., 2004, 279(34), 35630-35637.
9. Rowland, P.; Blaney, F.E.; Smyth, M.G.; Jones, J.J.; Leydon, V.R.; Oxbrow, A.K.; Lewis, C.J.; Tennant, M.G.; Modi, S.; Eggleston, D.S.; Chenery, R.J.; Bridges, A.M. Crystal structure of human cytochrome P450 2D6. J. Biol. Chem., 2006, 281(11), 7614-7622.
10. Porubsky, P.R.; Meneely, K.M.; Scott, E.E. Structures of human cytochrome P450 2E1. Insights into the binding of inhibitors and both small molecular weight and fatty acid substrates. J. Biol. Chem., 2008, 283(48), 33698-33707.
11. Strushkevich, N.; Usanov, S.A.; Plotnikov, A.N.; Jones, G.; Park, H.W. Structural analysis of CYP2R1 in complex with vitamin D3. J. Mol. Biol., 2008, 380(1), 95-106.
12. Williams, P.A.; Cosme, J.; Vinkovic, D.M.; Ward, A.; Angove, H.C.; Day, P.J.; Vonrhein, C.; Tickle, I.J.; Jhoti, H. Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science, 2004, 305(5684), 683-686.
13. Yano, J.K.; Wester, M.R.; Schoch, G.A.; Griffin, K.J.; Stout, C.D.; Johnson, E.F. The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-Å resolution. J. Biol. Chem., 2004, 279(37), 38091-38094.
14. Li, Y.C.; Chiang, C.W.; Yeh, H.C.; Hsu, P.Y.; Whitby, F.G.; Wang, L.H.; Chan, N.L. Structures of prostacyclin synthase and its complexes with substrate analog and inhibitor reveal a ligandspecific heme conformation change. J. Biol. Chem., 2008, 283(5), 2917-2926.
15. Mast, N.; White, M.A.; Bjorkhem, I.; Johnson, E.F.; Stout, C.D.; Pikuleva, I.A. Crystal structures of substrate-bound and substratefree cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain. Proc. Natl. Acad. Sci. U. S. A., 2008, 105(28), 9546-9551.
16. Romkes, M.; Faletto, M.B.; Blaisdell, J.A.; Raucy, J.L.; Goldstein, J.A. Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450 2C subfamily. Biochemistry (Mosc), 1991, 30(13), 3247-3255.
17. Gray, I.C.; Nobile, C.; Muresu, R.; Ford, S.; Spurr, N.K. A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24. Genomics, 1995, 28(2), 328-332.
18. Totah, R.A.; Rettie, A.E. Cytochrome P450 2C8: substrates, inhibitors, pharmacogenetics, and clinical relevance. Clin. Pharmacol. Ther., 2005, 77(5), 341-352.
19. Shimada, T.; Yamazaki, H.; Mimura, M.; Inui, Y.; Guengerich, F.P. Interindividual variations in human liver cytochrome P450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals. J. Pharmacol. Exp. Ther., 1994, 270(1), 414-423.
20. Zaphiropoulos, P.G. Exon skipping and circular RNA formation in transcripts of the human cytochrome P450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis. Mol. Cell. Biol., 1997, 17(6), 2985-2993.
21. Inoue, K.; Yamazaki, H.; Imiya, K.; Akasaka, S.; Guengerich, F.P.; Shimada, T. Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl hydroxylation and S-mephenytoin 4′-hydroxylation activities in livers of Japanese and Caucasian populations. Pharmacogenetics, 1997, 7(2), 103-113.
22. Shon, J.H.; Yoon, Y.R.; Kim, K.A.; Lim, Y.C.; Lee, K.J.; Park, J.Y.; Cha, I.J.; Flockhart, D.A.; Shin, J.G. Effects of CYP2C19 and CYP2C9 genetic polymorphisms on the disposition of and blood glucose lowering response to tolbutamide in humans. Pharmacogenetics, 2002, 12(2), 111-119.
23. Paine, M.F.; Hart, H.L.; Ludington, S.S.; Haining, R.L.; Rettie, A.E.; Zeldin, D.C. The human intestinal cytochrome P450 "pie". Drug Metab. Dispos., 2006, 34(5), 880-886.
24. Zhou, S.F.; Liu, J.P.; Chowbay, B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab. Rev., 2009, 41(2), 89-295.
25. Ravichandran, K.G.; Boddupalli, S.S.; Hasermann, C.A.; Peterson, J.A.; Deisenhofer, J. Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's. Science, 1993, 261(5122), 731-736.
26. Yamazaki, H.; Inoue, K.; Chiba, K.; Ozawa, N.; Kawai, T.; Suzuki, Y.; Goldstein, J.A.; Guengerich, F.P.; Shimada, T. Comparative studies on the catalytic roles of cytochrome P450 2C9 and its Cysand Leu-variants in the oxidation of warfarin, flurbiprofen, and diclofenac by human liver microsomes. Biochem. Pharmacol., 1998, 56(2), 243-251.
27. Giancarlo, G.M.; Venkatakrishnan, K.; Granda, B.W.; von Moltke, L.L.; Greenblatt, D.J. Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro: inhibition by sulfaphenazole, omeprazole, and ticlopidine. Eur. J. Clin. Pharmacol., 2001, 57(1), 31-36.
28. Lee, C.R.; Pieper, J.A.; Frye, R.F.; Hinderliter, A.L.; Blaisdell, J.A.; Goldstein, J.A. Tolbutamide, flurbiprofen, and losartan as probes of CYP2C9 activity in humans. J. Clin. Pharmacol., 2003, 43(1), 84-91.
29. Kumar, V.; Wahlstrom, J.L.; Rock, D.A.; Warren, C.J.; Gorman, L.A.; Tracy, T.S. CYP2C9 inhibition: impact of probe selection and pharmacogenetics on in vitro inhibition profiles. Drug Metab. Dispos., 2006, 34(12), 1966-1975.
30. Wester, M.R.; Lasker, J.M.; Johnson, E.F.; Raucy, J.L. CYP2C19 participates in tolbutamide hydroxylation by human liver microsomes. Drug Metab. Dispos., 2000, 28(3), 354-359.
31. Zgheib, N.K.; Frye, R.F.; Tracy, T.S.; Romkes, M.; Branch, R.A. Validation of incorporating flurbiprofen into the Pittsburgh cocktail. Clin. Pharmacol. Ther., 2006, 80(3), 257-263.
32. Crespi, C.L.; Stresser, D.M. Fluorometric screening for metabolism-based drug - drug interactions. J. Pharmacol. Toxicol. Methods, 2000, 44(1), 325-331.
33. Agundez, J.A.; Garcia-Martin, E.; Martinez, C. Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine? Expert. Opin. Drug Metab. Toxicol., 2009, 5(6), 607-620.
34. Zhou, S.F.; Zhou, Z.W.; Yang, L.P.; Cai, J.P. Substrates, inducers, inhibitors and structure-activity relationships of human cytochrome P450 2C9 and implications in drug development. Curr. Med. Chem., 2009, 16(27), 3480-3675.
35. Jeurissen, S.M.; Bogaards, J.J.; Awad, H.M.; Boersma, M.G.; Brand, W.; Fiamegos, Y.C.; van Beek, T.A.; Alink, G.M.; Sudholter, E.J.; Cnubben, N.H.; Rietjens, I.M. Human cytochrome P450 enzyme specificity for bioactivation of safrole to the proximate carcinogen 1′-hydroxysafrole. Chem. Res. Toxicol., 2004, 17(9), 1245-1250.
36. Ueng, Y.F.; Hsieh, C.H.; Don, M.J.; Chi, C.W.; Ho, L.K. Identification of the main human cytochrome P450 enzymes involved in safrole 1′- hydroxylation. Chem. Res. Toxicol., 2004, 17(8), 1151-1156.
37. Luo, G.; Qato, M.K.; Guenthner, T.M. Hydrolysis of the 2′,3′-allylic epoxides of allylbenzene, estragole, eugenol, and safrole by both microsomal and cytosolic epoxide hydrolases. Drug Metab. Dispos., 1992, 20(3), 440-445.
38. Randerath, K.; Putman, K.L.; Randerath, E. Flavor constituents in cola drinks induce hepatic DNA adducts in adult and fetal mice. Biochem. Biophys. Res. Commun., 1993, 192(1), 61-68.
39. Gupta, K.P.; van Golen, K.L.; Putman, K.L.; Randerath, K. Formation and persistence of safrole-DNA adducts over a 10,000-fold dose range in mouse liver. Carcinogenesis, 1993, 14(8), 1517-1521.
40. Liu, T.Y.; Chung, Y.T.; Wang, P.F.; Chi, C.W.; Hsieh, L.L. Safrole-DNA adducts in human peripheral blood - an association with areca quid chewing and CYP2E1 polymorphisms. Mutat. Res., 2004, 559(1-2), 59-66.
41. Lee, J.M.; Liu, T.Y.; Wu, D.C.; Tang, H.C.; Leh, J.; Wu, M.T.; Hsu, H.H.; Huang, P.M.; Chen, J.S.; Lee, C.J.; Lee, Y.C. Safrole-DNA adducts in tissues from esophageal cancer patients: clues to areca-related esophageal carcinogenesis. Mutat. Res., 2005, 565(2), 121-128.
42. Beyer, J.; Ehlers, D.; Maurer, H.H. Abuse of nutmeg (Myristica fragrans Houtt.): studies on the metabolism and the toxicologic detection of its ingredients elemicin, myristicin, and safrole in rat and human urine using gas chromatography/mass spectrometry. Ther. Drug Monit., 2006, 28(4), 568-575.
43. Miller, E.C.; Swanson, A.B.; Phillips, D.H.; Fletcher, T.L.; Liem, A.; Miller, J.A. Structure-activity studies of the carcinogenicities in the mouse and rat of some naturally occurring and synthetic alkenylbenzene derivatives related to safrole and estragole. Cancer Res., 1983, 43(3), 1124-1134.
44. Wiseman, R.W.; Miller, E.C.; Miller, J.A.; Liem, A. Structureactivity studies of the hepatocarcinogenicities of alkenylbenzene derivatives related to estragole and safrole on administration to preweanling male C57BL/6J x C3H/HeJ F1 mice. Cancer Res., 1987, 47(9), 2275-2283.
45. Jeurissen, S.M.; Bogaards, J.J.; Boersma, M.G.; ter Horst, J.P.; Awad, H.M.; Fiamegos, Y.C.; van Beek, T.A.; Alink, G.M.; Sudholter, E.J.; Cnubben, N.H.; Rietjens, I.M. Human cytochrome P450 enzymes of importance for the bioactivation of methyleugenol to the proximate carcinogen 1′- hydroxymethyleugenol. Chem. Res. Toxicol., 2006, 19(1), 111-116.
46. Gardner, I.; Wakazono, H.; Bergin, P.; de Waziers, I.; Beaune, P.; Kenna, J.G.; Caldwell, J. Cytochrome P450 mediated bioactivation of methyleugenol to 1′-hydroxymethyleugenol in Fischer 344 rat and human liver microsomes. Carcinogenesis, 1997, 18(9), 1775-1783.
47. Chan, V.S.; Caldwell, J. Comparative induction of unscheduled DNA synthesis in cultured rat hepatocytes by allylbenzenes and their 1′-hydroxy metabolites. Food Chem. Toxicol., 1992, 30(10), 831-836.
48. Howes, A.J.; Chan, V.S.; Caldwell, J. Structure-specificity of the genotoxicity of some naturally occurring alkenylbenzenes determined by the unscheduled DNA synthesis assay in rat hepatocytes. Food Chem. Toxicol., 1990, 28(8), 537-542.
49. Waddell, W.J.; Crooks, N.H.; Carmichael, P.L. Correlation of tumors with DNA adducts from methyl eugenol and tamoxifen in rats. Toxicol. Sci., 2004, 79(1), 38-40.
50. Miyazawa, M.; Shindo, M.; Shimada, T. Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab. Dispos., 2002, 30(5), 602-607.
51. Miyazawa, M.; Shindo, M.; Shimada, T. Sex differences in the metabolism of (+)- and (-)-limonene enantiomers to carveol and perillyl alcohol derivatives by cytochrome P450 enzymes in rat liver microsomes. Chem. Res. Toxicol., 2002, 15(1), 15-20.
52. Otake, Y.; Walle, T. Oxidation of the flavonoids galangin and kaempferide by human liver microsomes and CYP1A1, CYP1A2, and CYP2C9. Drug Metab. Dispos., 2002, 30(2), 103-105.
53. Ma, Q.; Lu, A.Y. CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies. Drug Metab. Dispos., 2007, 35(7), 1009-1016.
54. Yun, C.H.; Shimada, T.; Guengerich, F.P. Roles of human liver cytochrome P4502C and 3A enzymes in the 3-hydroxylation of benzo(a)pyrene. Cancer Res., 1992, 52(7), 1868-1874.
55. Shou, M.; Krausz, K.W.; Gonzalez, F.J.; Gelboin, H.V. Metabolic activation of the potent carcinogen dibenzo[a,h]anthracene by cDNA-expressed human cytochromes P450. Arch. Biochem. Biophys., 1996, 328(1), 201-207.
56. Stresser, D.M.; Kupfer, D. Human cytochrome P450-catalyzed conversion of the proestrogenic pesticide methoxychlor into an estrogen. Role of CYP2C19 and CYP1A2 in O-demethylation. Drug Metab. Dispos., 1998, 26(9), 868-874.
57. Scollon, E.J.; Starr, J.M.; Godin, S.J.; DeVito, M.J.; Hughes, M.F. In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome P450 isoforms. Drug Metab. Dispos., 2009, 37(1), 221-228.
58. Yamazaki, H.; Shimada, T. Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch. Biochem. Biophys., 1997, 346(1), 161-169.
59. Wang, B.; Sanchez, R.I.; Franklin, R.B.; Evans, D.C.; Huskey, S.E. The involvement of CYP3A4 and CYP2C9 in the metabolism of 17α- ethinylestradiol. Drug Metab. Dispos., 2004, 32(11), 1209-1212.
60. Ball, S.E.; Forrester, L.M.; Wolf, C.R.; Back, D.J. Differences in the cytochrome P450 isoenzymes involved in the 2-hydroxylation of oestradiol and 17α-ethinyloestradiol. Relative activities of rat and human liver enzymes. Biochem. J., 1990, 267(1), 221-226.
61. Marill, J.; Cresteil, T.; Lanotte, M.; Chabot, G.G. Identification of human cytochrome P450s involved in the formation of all-transretinoic acid principal metabolites. Mol. Pharmacol., 2000, 58(6), 1341-1348.
62. Rifkind, A.B.; Lee, C.; Chang, T.K.; Waxman, D.J. Arachidonic acid metabolism by human cytochrome P450s 2C8, 2C9, 2E1, and 1A2: regioselective oxygenation and evidence for a role for CYP2C enzymes in arachidonic acid epoxygenation in human liver microsomes. Arch. Biochem. Biophys., 1995, 320(2), 380-389.
63. Swinney, D.C. Progesterone metabolism in hepatic microsomes. Effect of the cytochrome P450 inhibitor, ketoconazole, and the NADPH 5α-reductase inhibitor, 4-MA, upon the metabolic profile in human, monkey, dog, and rat. Drug Metab. Dispos., 1990, 18(6), 859-865.
64. Choi, M.H.; Skipper, P.L.; Wishnok, J.S.; Tannenbaum, S.R. Characterization of testosterone 11??-hydroxylation catalyzed by human liver microsomal cytochromes P450. Drug Metab. Dispos., 2005, 33(6), 714-718.
65. Gentile, D.M.; Verhoeven, C.H.; Shimada, T.; Back, D.J. The role of CYP2C in the in vitro bioactivation of the contraceptive steroid desogestrel. J. Pharmacol. Exp. Ther., 1998, 287(3), 975-982.
66. Schmider, J.; Greenblatt, D.J.; von Moltke, L.L.; Karsov, D.; Vena, R.; Friedman, H.L.; Shader, R.I. Biotransformation of mestranol to ethinyl estradiol in vitro: the role of cytochrome P450 2C9 and metabolic inhibitors. J. Clin. Pharmacol., 1997, 37(3), 193-200.
67. Miners, J.O.; Birkett, D.J. Cytochrome P450 2C9: an enzyme of major importance in human drug metabolism. Br. J. Clin. Pharmacol., 1998, 45(6), 525-538.
68. Bajpai, M.; Roskos, L.K.; Shen, D.D.; Levy, R.H. Roles of cytochrome P4502C9 and cytochrome P4502C19 in the stereoselective metabolism of phenytoin to its major metabolite. Drug Metab. Dispos., 1996, 24(12), 1401-1403.
69. Rahman, A.; Korzekwa, K.R.; Grogan, J.; Gonzalez, F.J.; Harris, J.W. Selective biotransformation of taxol to 6 α-hydroxytaxol by human cytochrome P450 2C8. Cancer Res., 1994, 54(21), 5543-5546.
70. Cresteil, T.; Monsarrat, B.; Dubois, J.; Sonnier, M.; Alvinerie, P.; Gueritte, F. Regioselective metabolism of taxoids by human CYP3A4 and 2C8: structure-activity relationship. Drug Metab. Dispos., 2002, 30(4), 438-445.
71. Li, X.Q.; Bjorkman, A.; Andersson, T.B.; Ridderstrom, M.; Masimirembwa, C.M. Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate. J. Pharmacol. Exp. Ther., 2002, 300(2), 399-407.
72. Projean, D.; Baune, B.; Farinotti, R.; Flinois, J.P.; Beaune, P.; Taburet, A.M.; Ducharme, J. In vitro metabolism of chloroquine: identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation. Drug Metab. Dispos., 2003, 31(6), 748-754.
73. Baldwin, S.J.; Clarke, S.E.; Chenery, R.J. Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone. Br. J. Clin. Pharmacol., 1999, 48(3), 424-432.
74. Jaakkola, T.; Laitila, J.; Neuvonen, P.J.; Backman, J.T. Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin. Pharmacol. Toxicol., 2006, 99(1), 44-51.
75. Becquemont, L.; Mouajjah, S.; Escaffre, O.; Beaune, P.; Funck-Brentano, C.; Jaillon, P. Cytochrome P-450 3A4 and 2C8 are involved in zopiclone metabolism. Drug Metab. Dispos., 1999, 27(9), 1068-1073.
76. Hamman, M.A.; Thompson, G.A.; Hall, S.D. Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C. Biochem. Pharmacol., 1997, 54(1), 33-41.
77. Wienkers, L.C.; Wurden, C.J.; Storch, E.; Kunze, K.L.; Rettie, A.E.; Trager, W.F. Formation of (R)-8-hydroxywarfarin in human liver microsomes. A new metabolic marker for the (S)-mephenytoin hydroxylase, P4502C19. Drug Metab. Dispos., 1996, 24(5), 610-614.
78. Rettie, A.E.; Korzekwa, K.R.; Kunze, K.L.; Lawrence, R.F.; Eddy, A.C.; Aoyama, T.; Gelboin, H.V.; Gonzalez, F.J.; Trager, W.F. Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of S-warfarin-drug interactions. Chem. Res. Toxicol., 1992, 5(1), 54-59.
79. Jung, F.; Griffin, K.J.; Song, W.; Richardson, T.H.; Yang, M.; Johnson, E.F. Identification of amino acid substitutions that confer a high affinity for sulfaphenazole binding and a high catalytic efficiency for warfarin metabolism to P450 2C19. Biochemistry (Mosc), 1998, 37(46), 16270-16279.
80. 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(6), 587-594.
81. Saller, R.; Brignoli, R.; Melzer, J.; Meier, R. An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forsch. Komplementmed., 2008, 15(1), 9-20.
82. Saller, R.; Meier, R.; Brignoli, R. The use of silymarin in the treatment of liver diseases. Drugs, 2001, 61(14), 2035-2063.
83. Gazak, R.; Walterova, D.; Kren, V. Silybin and silymarin - new and emerging applications in medicine. Curr. Med. Chem., 2007, 14(3), 315-338.
84. Jancova, P.; Anzenbacherova, E.; Papouskova, B.; Lemr, K.; Luzna, P.; Veinlichova, A.; Anzenbacher, P.; Simanek, V. Silybin is metabolized by cytochrome P450 2C8 in vitro. Drug Metab. Dispos., 2007, 35(11), 2035-2039.
85. Han, Y.; Guo, D.; Chen, Y.; Chen, Y.; Tan, Z.R.; Zhou, H.H. Effect of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 in healthy Chinese volunteers. Eur. J. Clin. Pharmacol., 2009, 65(6), 585-591.
86. Lopez-Garcia, M.P.; Dansette, P.M.; Mansuy, D. Thiophene derivatives as new mechanism-based inhibitors of cytochromes P450: inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic acid. Biochemistry (Mosc), 1994, 33(1), 166-175.
87. Dansette, P.M.; Amar, C.; Smith, C.; Pons, C.; Mansuy, D. Oxidative activation of the thiophene ring by hepatic enzymes. Hydroxylation and formation of electrophilic metabolites during metabolism of tienilic acid and its isomer by rat liver microsomes. Biochem. Pharmacol., 1990, 39(5), 911-918.
88. Belghazi, M.; Jean, P.; Poli, S.; Schmitter, J.M.; Mansuy, D.; Dansette, P.M. Use of isotopes and LC-MS-ESI-TOF for mechanistic studies of tienilic acid metabolic activation. Adv. Exp. Med. Biol., 2001, 500, 139-144.
89. Lopez Garcia, M.P.; Dansette, P.M.; Valadon, P.; Amar, C.; Beaune, P.H.; Guengerich, F.P.; Mansuy, D. Human-liver cytochromes P-450 expressed in yeast as tools for reactivemetabolite formation studies. Oxidative activation of tienilic acid by cytochromes P-450 2C9 and 2C10. Eur. J. Biochem., 1993, 213(1), 223-232.
90. Bonierbale, E.; Valadon, P.; Pons, C.; Desfosses, B.; Dansette, P.M.; Mansuy, D. Opposite behaviors of reactive metabolites of tienilic acid and its isomer toward liver proteins: use of specific anti-tienilic acid-protein adduct antibodies and the possible relationship with different hepatotoxic effects of the two compounds. Chem. Res. Toxicol., 1999, 12(3), 286-296.
91. Mancy, A.; Broto, P.; Dijols, S.; Dansette, P.M.; Mansuy, D. The substrate binding site of human liver cytochrome P450 2C9: an approach using designed tienilic acid derivatives and molecular modeling. Biochemistry (Mosc), 1995, 34(33), 10365-10375.
92. O'Donnell, J.P.; Dalvie, D.K.; Kalgutkar, A.S.; Obach, R.S. Mechanism-based inactivation of human recombinant P450 2C9 by the nonsteroidal anti-inflammatory drug suprofen. Drug Metab. Dispos., 2003, 31(11), 1369-1377.
93. Kamiyama, E.; Yoshigae, Y.; Kasuya, A.; Takei, M.; Kurihara, A.; Ikeda, T. Inhibitory effects of angiotensin receptor blockers on CYP2C9 activity in human liver microsomes. Drug Metab. Pharmacokinet., 2007, 22(4), 267-275.
94. Taavitsainen, P.; Kiukaanniemi, K.; Pelkonen, O. In vitro inhibition screening of human hepatic P450 enzymes by five angiotensin-II receptor antagonists. Eur. J. Clin. Pharmacol., 2000, 56(2), 135-140.
95. Voorman, R.L.; Payne, N.A.; Wienkers, L.C.; Hauer, M.J.; Sanders, P.E. Interaction of delavirdine with human liver microsomal cytochrome P450: inhibition of CYP2C9, CYP2C19, and CYP2D6. Drug Metab. Dispos., 2001, 29(1), 41-47.
96. Voorman, R.L.; Maio, S.M.; Hauer, M.J.; Sanders, P.E.; Payne, N.A.; Ackland, M.J. Metabolism of delavirdine, a human immunodeficiency virus type-1 reverse transcriptase inhibitor, by microsomal cytochrome P450 in humans, rats, and other species: probable involvement of CYP2D6 and CYP3A. Drug Metab. Dispos., 1998, 26(7), 631-639.
97. Miners, J.O.; Smith, K.J.; Robson, R.A.; McManus, M.E.; Veronese, M.E.; Birkett, D.J. Tolbutamide hydroxylation by human liver microsomes. Kinetic characterisation and relationship to other cytochrome P-450 dependent xenobiotic oxidations. Biochem. Pharmacol., 1988, 37(6), 1137-1144.
98. Pond, S.M.; Birkett, D.J.; Wade, D.N. Mechanisms of inhibition of tolbutamide metabolism: phenylbutazone, oxyphenbutazone, sulfaphenazole. Clin. Pharmacol. Ther., 1977, 22(5 Pt 1), 573-579.
99. Kim, K.A.; Park, J.Y. Inhibitory effect of glyburide on human cytochrome P450 isoforms in human liver microsomes. Drug Metab. Dispos., 2003, 31(9), 1090-1092.
100. Wen, X.; Wang, J.S.; Backman, J.T.; Kivisto, K.T.; Neuvonen, P.J. Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9. Drug Metab. Dispos., 2001, 29(11), 1359-1361.
101. Kunze, K.L.; Wienkers, L.C.; Thummel, K.E.; Trager, W.F. Warfarin-fluconazole. I. Inhibition of the human cytochrome P450-dependent metabolism of warfarin by fluconazole: in vitro studies. Drug Metab. Dispos., 1996, 24(4), 414-421.
102. Yamazaki, H.; Shimada, T. Human liver cytochrome P450 enzymes involved in the 7-hydroxylation of R- and S-warfarin enantiomers. Biochem. Pharmacol., 1997, 54(11), 1195-1203.
103. Iwakawa, S.; Miyashita, K.; Hashimoto, Y.; Kuroda, T. Effect of glimepiride and glibenclamide on S-warfarin 7-hydroxylation by human liver microsomes, recombinant human CYP2C9.1 and CYP2C9.3. Biol. Pharm. Bull., 2006, 29(9), 1983-1985.
104. Islam, S.I.; Masuda, Q.N.; Bolaji, O.O.; Shaheen, F.M.; Sheikh, I.A. Possible interaction between cyclosporine and glibenclamide in posttransplant diabetic patients. Ther. Drug Monit., 1996, 18(5), 624-626.
105. Jassel, S.V. Drug points. Br. Med. J., 1991, 303(789.
106. Asplund, K.; Wiholm, B.E.; Lithner, F. Glibenclamide-associated hypoglycaemia: a report on 57 cases. Diabetologia, 1983, 24(6), 412-417.
107. Kubacka, R.T.; Antal, E.J.; Juhl, R.P. The paradoxical effect of cimetidine and ranitidine on glibenclamide pharmacokinetics and pharmacodynamics. Br. J. Clin. Pharmacol., 1987, 23(6), 743-751.
108. Loupi, E.; Descotes, J.; Lery, N.; Evreux, J.C. [Drug interactions involving miconazole]. Therapie, 1982, 37(4), 437-441.
109. Albengres, E.; Le Louet, H.; Tillement, J.P. Systemic antifungal agents. Drug interactions of clinical significance. Drug Saf., 1998, 18(2), 83-97.
110. Ahmad, S. Gemfibrozil: interaction with glyburide. South Med. J., 1991, 84(1), 102.
111. Li, X.Q.; Andersson, T.B.; Ahlstrom, M.; Weidolf, L. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab. Dispos., 2004, 32(8), 821-827.
112. Back, D.J.; Tjia, J.F.; Karbwang, J.; Colbert, J. In vitro inhibition studies of tolbutamide hydroxylase activity of human liver microsomes by azoles, sulphonamides and quinolines. Br. J. Clin. Pharmacol., 1988, 26(1), 23-29.
113. Zhang, W.; Ramamoorthy, Y.; Kilicarslan, T.; Nolte, H.; Tyndale, R.F.; Sellers, E.M. Inhibition of cytochromes P450 by antifungal imidazole derivatives. Drug Metab. Dispos., 2002, 30(3), 314-318.
114. Baldwin, S.J.; Bloomer, J.C.; Smith, G.J.; Ayrton, A.D.; Clarke, S.E.; Chenery, R.J. Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503A and 2C9. Xenobiotica, 1995, 25(3), 261-270.
115. Back, D.J.; Stevenson, P.; Tjia, J.F. Comparative effects of two antimycotic agents, ketoconazole and terbinafine on the metabolism of tolbutamide, ethinyloestradiol, cyclosporin and ethoxycoumarin by human liver microsomes in vitro. Br. J. Clin. Pharmacol., 1989, 28(2), 166-170.
116. Bourrie, M.; Meunier, V.; Berger, Y.; Fabre, G. Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes. J. Pharmacol. Exp. Ther., 1996, 277(1), 321-332.
117. Sai, Y.; Dai, R.; Yang, T.J.; Krausz, K.W.; Gonzalez, F.J.; Gelboin, H.V.; Shou, M. Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450. Xenobiotica, 2000, 30(4), 327-343.
118. Venkatakrishnan, K.; von Moltke, L.L.; Greenblatt, D.J. Effects of the antifungal agents on oxidative drug metabolism: clinical relevance. Clin. Pharmacokinet., 2000, 38(2), 111-180.
119. Touchette, M.A.; Chandrasekar, P.H.; Milad, M.A.; Edwards, D.J. Contrasting effects of fluconazole and ketoconazole on phenytoin and testosterone disposition in man. Br. J. Clin. Pharmacol., 1992, 34(1), 75-78.
120. Transon, C.; Leemann, T.; Dayer, P. In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur. J. Clin. Pharmacol., 1996, 50(3), 209-215.
121. Fischer, V.; Johanson, L.; Heitz, F.; Tullman, R.; Graham, E.; Baldeck, J.P.; Robinson, W.T. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P450 and implications for metabolic drug interactions. Drug Metab. Dispos., 1999, 27(3), 410-416.
122. Transon, C.; Leemann, T.; Vogt, N.; Dayer, P. In vivo inhibition profile of cytochrome P450TB (CYP2C9) by (±)-fluvastatin. Clin. Pharmacol. Ther., 1995, 58(4), 412-417.
123. Rindone, J.P.; Keng, H.C. Gemfibrozil-warfarin drug interaction resulting in profound hypoprothrombinemia. Chest, 1998, 114(2), 641-642.
124. Newton, D.J.; Wang, R.W.; Lu, A.Y. Cytochrome P450 inhibitors. Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab. Dispos., 1995, 23(1), 154-158.
125. Veronese, M.E.; Mackenzie, P.I.; Doecke, C.J.; McManus, M.E.; Miners, J.O.; Birkett, D.J. Tolbutamide and phenytoin hydroxylations by cDNA-expressed human liver cytochrome P4502C9. Biochem. Biophys. Res. Commun., 1991, 175(3), 1112-1118.
126. Veronese, M.E.; Miners, J.O.; Randles, D.; Gregov, D.; Birkett, D.J. Validation of the tolbutamide metabolic ratio for population screening with use of sulfaphenazole to produce model phenotypic poor metabolizers. Clin. Pharmacol. Ther., 1990, 47(3), 403-411.
127. Mancy, A.; Dijols, S.; Poli, S.; Guengerich, P.; Mansuy, D. Interaction of sulfaphenazole derivatives with human liver cytochromes P450 2C: molecular origin of the specific inhibitory effects of sulfaphenazole on CYP2C9 and consequences for the substrate binding site topology of CYP2C9. Biochemistry (Mosc), 1996, 35(50), 16205-16212.
128. Zhou, S.; Gao, Y.; Jiang, W.; Huang, M.; Xu, A.; Paxton, J.W. Interactions of herbs with cytochrome P450. Drug Metab. Rev., 2003, 35(1), 35-98.
129. Volak, L.P.; Ghirmai, S.; Cashman, J.R.; Court, M.H. Curcuminoids inhibit multiple human cytochromes P450, UDPglucuronosyltransferase, and sulfotransferase enzymes, whereas piperine is a relatively selective CYP3A4 inhibitor. Drug Metab. Dispos., 2008, 36(8), 1594-1605.
130. Kim, J.Y.; Lee, S.; Kim, D.H.; Kim, B.R.; Park, R.; Lee, B.M. Effects of flavonoids isolated from Scutellariae radix on cytochrome P450 activities in human liver microsomes. J. Toxicol. Environ. Health A, 2002, 65(5-6), 373-381.
131. Foti, R.S.; Wahlstrom, J.L.; Wienkers, L.C. The in vitro drug interaction potential of dietary supplements containing multiple herbal components. Drug Metab. Dispos., 2007, 35(2), 185-188.
132. von Moltke, L.L.; Weemhoff, J.L.; Bedir, E.; Khan, I.A.; Harmatz, J.S.; Goldman, P.; Greenblatt, D.J. Inhibition of human cytochromes P450 by components of Ginkgo biloba. J. Pharm. Pharmacol., 2004, 56(8), 1039-1044.
133. Gaudineau, C.; Beckerman, R.; Welbourn, S.; Auclair, K. Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. Biochem. Biophys. Res. Commun., 2004, 318(4), 1072-1078.
134. Zou, L.; Harkey, M.R.; Henderson, G.L. Effects of herbal components on cDNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci., 2002, 71(13), 1579-1589.
135. 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 human liver microsomes. Drug Metab. Dispos., 2008, 36(7), 1308-1314.
136. Izzat, M.B.; Yim, A.P.C.; El-Zufari, M.H. A taste of Chinese medicine! Ann. Thorac. Surg., 1998, 66(941-942.
137. 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's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc. Natl. Acad. Sci. U. S. A., 2000, 97(13), 7500-7502.
138. 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(3), 427-431.
139. Wentworth, J.M.; Agostini, M.; Love, J.; Schwabe, J.W.; Chatterjee, V.K. St John's wort, a herbal antidepressant, activates the steroid X receptor. J. Endocrinol., 2000, 166(3), R11-16.
140. Obach, R.S. Inhibition of human cytochrome P450 enzymes by constituents of St. John's wort, an herbal preparation used in the treatment of depression. J. Pharmacol. Exp. Ther., 2000, 294(1), 88-95.
141. 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) on human cytochrome P450 activity. Clin. Pharmacol. Ther., 2001, 70(4), 317-326.
142. 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(5), 451-457.
143. Liu, K.H.; Kim, M.J.; Jeon, B.H.; Shon, J.H.; Cha, I.J.; Cho, K.H.; Lee, S.S.; Shin, J.G. Inhibition of human cytochrome P450 isoforms and NADPH-CYP reductase in vitro by 15 herbal medicines, including Epimedii herba. J. Clin. Pharm. Ther., 2006, 31(1), 83-91.
144. Guengerich, F.P.; Shimada, T.; Umbenhauer, D.R.; Martin, M.V.; Misono, K.S.; Distlerath, L.M.; Reilly, P.E.; Wolff, T. Structure and function of cytochrome P-450. Adv. Exp. Med. Biol., 1986, 197, 83-94.
145. Smith, D.A.; Jones, B.C. Speculations on the substrate structureactivity
146. Jones, B.C.; Hawksworth, G.; Horne, V.A.; Newlands, A.; Tute, M.S.; Smith, D.A. Putative active site model for P4502C9 (tolbutamide hydroxylase). Br. J. Clin. Pharmacol., 1993, 34(Suppl), P143-P144.
147. Jones, B.C.; Hawksworth, G.; Horne, V.A.; Newlands, A.; Morsman, J.; Tute, M.S.; Smith, D.A. Putative active site template model for cytochrome P4502C9 (tolbutamide hydroxylase). Drug Metab. Dispos., 1996, 24(2), 260-266.
148. Ridderstrom, M.; Masimirembwa, C.; Trump-Kallmeyer, S.; Ahlefelt, M.; Otter, C.; Andersson, T.B. Arginines 97 and 108 in CYP2C9 are important determinants of the catalytic function. Biochem. Biophys. Res. Commun., 2000, 270(3), 983-987.
149. Poli-Scaife, S.; Attias, R.; Dansette, P.M.; Mansuy, D. The substrate binding site of human liver cytochrome P450 2C9: an NMR study. Biochemistry (Mosc), 1997, 36(42), 12672-12682.
150. Ekins, S.; Bravi, G.; Binkley, S.; Gillespie, J.S.; Ring, B.J.; Wikel, J.H.; Wrighton, S.A. Three- and four-dimensional-quantitative structure activity relationship (3D/4D-QSAR) analyses of CYP2C9 inhibitors. Drug Metab. Dispos., 2000, 28(8), 994-1002.
151. Jones, J.P.; He, M.; Trager, W.F.; Rettie, A.E. Three-dimensional quantitative structure-activity relationship for inhibitors of cytochrome P4502C9. Drug Metab. Dispos., 1996, 24(1), 1-6.
152. Lewis, D.F.; Dickins, M.; Weaver, R.J.; Eddershaw, P.J.; Goldfarb, P.S.; Tarbit, M.H. Molecular modelling of human CYP2C subfamily enzymes CYP2C9 and CYP2C19: rationalization of substrate specificity and site-directed mutagenesis experiments in the CYP2C subfamily. Xenobiotica, 1998, 28(3), 235-268.
153. Haining, R.L.; Jones, J.P.; Henne, K.R.; Fisher, M.B.; Koop, D.R.; Trager, W.F.; Rettie, A.E. Enzymatic determinants of the substrate specificity of CYP2C9: role of B'-C loop residues in providing the π-stacking anchor site for warfarin binding. Biochemistry (Mosc), 1999, 38(11), 3285-3292.
154. Tracy, T.S.; Marra, C.; Wrighton, S.A.; Gonzalez, F.J.; Korzekwa, K.R. Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation. Eur. J. Clin. Pharmacol., 1997, 52(4), 293-298.
155. Korzekwa, K.R.; Krishnamachary, N.; Shou, M.; Ogai, A.; Parise, R.A.; Rettie, A.E.; Gonzalez, F.J.; Tracy, T.S. Evaluation of atypical cytochrome P450 kinetics with two-substrate models: evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry (Mosc), 1998, 37(12), 4137-4147.
156. de Groot, M.J.; Alex, A.A.; Jones, B.C. Development of a combined protein and pharmacophore model for cytochrome P450 2C9. J. Med. Chem., 2002, 45(10), 1983-1993.
157. Berellini, G.; Cruciani, G.; Mannhold, R. Pharmacophore, drug metabolism, and pharmacokinetics models on non-peptide AT1, AT2, and AT1/AT2 angiotensin II receptor antagonists. J. Med. Chem., 2005, 48(13), 4389-4399.
158. Takahashi, H.; Sato, T.; Shimoyama, Y.; Shioda, N.; Shimizu, T.; Kubo, S.; Tamura, N.; Tainaka, H.; Yasumori, T.; Echizen, H. Potentiation of anticoagulant effect of warfarin caused by enantioselective metabolic inhibition by the uricosuric agent benzbromarone. Clin. Pharmacol. Ther., 1999, 66(6), 569-581.
159. O'Reilly, R.A.; Trager, W.F.; Rettie, A.E.; Goulart, D.A. Interaction of amiodarone with racemic warfarin and its separated enantiomorphs in humans. Clin. Pharmacol. Ther., 1987, 42(3), 290-294.
160. Locuson, C.W., 2nd; Wahlstrom, J.L.; Rock, D.A.; Rock, D.A.; Jones, J.P. A new class of CYP2C9 inhibitors: probing 2C9 specificity with high-affinity benzbromarone derivatives. Drug Metab. Dispos., 2003, 31(7), 967-971.
161. Locuson, C.W.; Wahlstrom, J.L. Three-dimensional quantitative structure-activity relationship analysis of cytochromes p450: effect of incorporating higher-affinity ligands and potential new applications. Drug Metab. Dispos., 2005, 33(7), 873-878.
162. Shimodaira, H.; Takahashi, K.; Kano, K.; Matsumoto, Y.; Uchida, Y.; Kudo, T. Enhancement of anticoagulant action by warfarinbenzbromarone interaction. J. Clin. Pharmacol., 1996, 36(2), 168-174.
163. Zhang, Z.Y.; Kerr, J.; Wexler, R.S.; Li, H.Y.; Robinson, A.J.; Harlow, P.P.; Kaminsky, L.S. Warfarin analog inhibition of human CYP2C9-catalyzed S-warfarin 7-hydroxylation. Thromb. Res., 1997, 88(4), 389-398.
164. Mancy, A.; Antignac, M.; Minoletti, C.; Dijols, S.; Mouries, V.; Duong, N.T.; Battioni, P.; Dansette, P.M.; Mansuy, D. Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry (Mosc), 1999, 38(43), 14264-14270.
165. Kalgutkar, A.S.; Crews, B.C.; Rowlinson, S.W.; Marnett, A.B.; Kozak, K.R.; Remmel, R.P.; Marnett, L.J. Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors: facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors. Proc. Natl. Acad. Sci. U. S. A., 2000, 97(2), 925-930.
166. Kalgutkar, A.S.; Marnett, A.B.; Crews, B.C.; Remmel, R.P.; Marnett, L.J. Ester and amide derivatives of the nonsteroidal antiinflammatory drug, indomethacin, as selective cyclooxygenase-2 inhibitors. J. Med. Chem., 2000, 43(15), 2860-2870.
167. Remmel, R.P.; Crews, B.C.; Kozak, K.R.; Kalgutkar, A.S.; Marnett, L.J. Studies on the metabolism of the novel, selective cyclooxygenase-2 inhibitor indomethacin phenethylamide in rat, mouse, and human liver microsomes: identification of active metabolites. Drug Metab. Dispos., 2004, 32(1), 113-122.
168. Boyer, D.; Bauman, J.N.; Walker, D.P.; Kapinos, B.; Karki, K.; Kalgutkar, A.S. Utility of MetaSite in improving metabolic stability of the neutral indomethacin amide derivative and selective cyclooxygenase-2 inhibitor 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl) -N-phenethyl-aceta mide. Drug Metab. Dispos., 2009, 37(5), 999-1008.
169. Cruciani, G.; Carosati, E.; De Boeck, B.; Ethirajulu, K.; Mackie, C.; Howe, T.; Vianello, R. MetaSite: understanding metabolism in human cytochromes from the perspective of the chemist. J. Med. Chem., 2005, 48(22), 6970-6979.
170. Komatsu, K.; Ito, K.; Nakajima, Y.; Kanamitsu, S.; Imaoka, S.; Funae, Y.; Green, C.E.; Tyson, C.A.; Shimada, N.; Sugiyama, Y. Prediction of in vivo drug-drug interactions between tolbutamide and various sulfonamides in humans based on in vitro experiments. Drug Metab. Dispos., 2000, 28(4), 475-481.
171. Marques-Soares, C.; Dijols, S.; Macherey, A.C.; Wester, M.R.; Johnson, E.F.; Dansette, P.M.; Mansuy, D. Sulfaphenazole derivatives as tools for comparing cytochrome P450 2C5 and human cytochromes P450 2Cs: identification of a new high affinity substrate common to those enzymes. Biochemistry (Mosc), 2003, 42(21), 6363-6369.
172. Kumar, V.; Locuson, C.W.; Sham, Y.Y.; Tracy, T.S. Amiodarone analog-dependent effects on CYP2C9-mediated metabolism and kinetic profiles. Drug Metab. Dispos., 2006, 34(10), 1688-1696.
173. Locuson, C.W., 2nd; Rock, D.A.; Jones, J.P. Quantitative binding models for CYP2C9 based on benzbromarone analogues. Biochemistry (Mosc), 2004, 43(22), 6948-6958.
174. Ahlstrom, M.M.; Ridderstrom, M.; Zamora, I. CYP2C9 structuremetabolism relationships: substrates, inhibitors, and metabolites. J. Med. Chem., 2007, 50(22), 5382-5391.
175. Sandberg, M.; Yasar, U.; Stromberg, P.; Hoog, J.O.; Eliasson, E. Oxidation of celecoxib by polymorphic cytochrome P450 2C9 and alcohol dehydrogenase. Br. J. Clin. Pharmacol., 2002, 54(4), 423-429.
176. Tang, C.; Shou, M.; Mei, Q.; Rushmore, T.H.; Rodrigues, A.D. Major role of human liver microsomal cytochrome P450 2C9 (CYP2C9) in the oxidative metabolism of celecoxib, a novel cyclooxygenase-II inhibitor. J. Pharmacol. Exp. Ther., 2000, 293(2), 453-459.
177. Ahlstrom, M.M.; Ridderstrom, M.; Zamora, I.; Luthman, K. CYP2C9 structure-metabolism relationships: optimizing the metabolic stability of COX-2 inhibitors. J. Med. Chem., 2007, 50(18), 4444-4452.
178. Peng, C.C.; Cape, J.L.; Rushmore, T.; Crouch, G.J.; Jones, J.P. Cytochrome P450 2C9 type II binding studies on quinoline-4-carboxamide analogues. J. Med. Chem., 2008, 51(24), 8000-8011.
179. Hudelson, M.G.; Ketkar, N.S.; Holder, L.B.; Carlson, T.J.; Peng, C.C.; Waldher, B.J.; Jones, J.P. High confidence predictions of drug-drug interactions: predicting affinities for cytochrome P450 2C9 with multiple computational methods. J. Med. Chem., 2008, 51(3), 648-654.
180. Si, D.; Wang, Y.; Zhou, Y.H.; Guo, Y.; Wang, J.; Zhou, H.; Li, Z.S.; Fawcett, J.P. Mechanism of CYP2C9 inhibition by flavones and flavonols. Drug Metab. Dispos., 2009, 37(3), 629-634.
181. Weaver, R.J.; Dickins, M.; Burke, M.D. Hydroxylation of the antimalarial drug 58C80 by CYP2C9 in human liver microsomes: comparison with mephenytoin and tolbutamide hydroxylations. Biochem. Pharmacol., 1995, 49(7), 997-1004.
182. Machinist, J.M.; Mayer, M.D.; Roberts, E.M.; Surber, B.W.; Rodrigues, A.D. Identification of the human liver cytochrome P450 enzymes involved in the in vitro metabolism of a novel 5-lipoxygenase inhibitor. Drug Metab. Dispos., 1998, 26(10), 970-976.
183. Bort, R.; Ponsoda, X.; Carrasco, E.; Gomez-Lechon, M.J.; Castell, J.V. Comparative metabolism of the nonsteroidal antiinflammatory drug, aceclofenac, in the rat, monkey, and human. Drug Metab. Dispos., 1996, 24(9), 969-975.
184. Thijssen, H.H.; Flinois, J.P.; Beaune, P.H. Cytochrome P4502C9 is the principal catalyst of racemic acenocoumarol hydroxylation reactions in human liver microsomes. Drug Metab. Dispos., 2000, 28(11), 1284-1290.
185. Laine, J.E.; Auriola, S.; Pasanen, M.; Juvonen, R.O. Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. Xenobiotica, 2009, 39(1), 11-21.
186. Leemann, T.; Kondo, M.; Zhao, J.; Transon, C.; Bonnabry, P.; Dayer, P. [The biotransformation of NSAIDs: a common elimination site and drug interactions]. Schweiz. Med. Wochenschr., 1992, 122(49), 1897-1899.
187. Cotreau-Bibbo, M.M.; von Moltke, L.L.; Greenblatt, D.J. Influence of polyethylene glycol and acetone on the in vitro biotransformation of tamoxifen and alprazolam by human liver microsomes. J. Pharm. Sci., 1996, 85(11), 1180-1185.
188. Komori, M.; Hashizume, T.; Ohi, H.; Miura, T.; Kitada, M.; Nagashima, K.; Kamataki, T. Cytochrome P450 in human liver microsomes: high-performance liquid chromatographic isolation of three forms and their characterization. J. Biochem., 1988, 104(6), 912-916.
189. Ohyama, K.; Nakajima, M.; Nakamura, S.; Shimada, N.; Yamazaki, H.; Yokoi, T. A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor. Drug Metab. Dispos., 2000, 28(11), 1303-1310.
190. Mellstrom, B.; von Bahr, C. Demethylation and hydroxylation of amitriptyline, nortriptyline, and 10-hydroxyamitriptyline in human liver microsomes. Drug Metab. Dispos., 1981, 9(6), 565-568.
191. Decker, C.J.; Laitinen, L.M.; Bridson, G.W.; Raybuck, S.A.; Tung, R.D.; Chaturvedi, P.R. Metabolism of amprenavir in liver microsomes: role of CYP3A4 inhibition for drug interactions. J. Pharm. Sci., 1998, 87(7), 803-807.
192. Treluyer, J.M.; Bowers, G.; Cazali, N.; Sonnier, M.; Rey, E.; Pons, G.; Cresteil, T. Oxidative metabolism of amprenavir in the human liver. Effect of the CYP3A maturation. Drug Metab. Dispos., 2003, 31(3), 275-281.
193. Engel, G.; Hofmann, U.; Heidemann, H.; Cosme, J.; Eichelbaum, M. Antipyrine as a probe for human oxidative drug metabolism: identification of the cytochrome P450 enzymes catalyzing 4-hydroxyantipyrine, 3- hydroxymethylantipyrine, and norantipyrine formation. Clin. Pharmacol. Ther., 1996, 59(6), 613-623.
194. Grace, J.M.; Skanchy, D.J.; Aguilar, A.J. Metabolism of artelinic acid to dihydroqinqhaosu by human liver cytochrome P4503A. Xenobiotica, 1999, 29(7), 703-717.
195. Nakajima, M.; Nakamura, S.; Tokudome, S.; Shimada, N.; Yamazaki, H.; Yokoi, T. Azelastine N-demethylation by CYP3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab. Dispos., 1999, 27(12), 1381-1391.
196. Pekol, T.; Daniels, J.S.; Labutti, J.; Parsons, I.; Nix, D.; Baronas, E.; Hsieh, F.; Gan, L.S.; Miwa, G. Human metabolism of the proteasome inhibitor bortezomib: identification of circulating metabolites. Drug Metab. Dispos., 2005, 33(6), 771-777.
197. Dingemanse, J.; van Giersbergen, P.L. Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clin. Pharmacokinet., 2004, 43(15), 1089-1115.
198. Zanger, U.M.; Raimundo, S.; Eichelbaum, M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch. Pharmacol., 2004, 369(1), 23-37.
199. Picard, N.; Cresteil, T.; Djebli, N.; Marquet, P. In vitro metabolism study of buprenorphine: evidence for new metabolic pathways. Drug Metab. Dispos., 2005, 33(5), 689-695.
200. Kot, M.; Daniel, W.A. The relative contribution of human cytochrome P450 isoforms to the four caffeine oxidation pathways: an in vitro comparative study with cDNA-expressed P450s including CYP2C isoforms. Biochem. Pharmacol., 2008, 76(4), 543-551.
201. Hanatani, T.; Fukuda, T.; Ikeda, M.; Imaoka, S.; Hiroi, T.; Funae, Y.; Azuma, J. CYP2C9*3 influences the metabolism and the druginteraction of candesartan in vitro. Pharmacogenomics J., 2001, 1(4), 288-292.
202. Oldham, H.G.; Clarke, S.E. In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilol. Drug Metab. Dispos., 1997, 25(8), 970-977.
203. Helsby, N.A.; Ward, S.A.; Howells, R.E.; Breckenridge, A.M. In vitro metabolism of the biguanide antimalarials in human liver microsomes: evidence for a role of the mephenytoin hydroxylase (P450 MP) enzyme. Br. J. Clin. Pharmacol., 1990, 30(2), 287-291.
204. Shon, J.H.; Yoon, Y.R.; Kim, M.J.; Kim, K.A.; Lim, Y.C.; Liu, K.H.; Shin, D.H.; Lee, C.H.; Cha, I.J.; Shin, J.G. Chlorpropamide 2-hydroxylation is catalysed by CYP2C9 and CYP2C19 in vitro: chlorpropamide disposition is influenced by CYP2C9, but not by CYP2C19 genetic polymorphism. Br. J. Clin. Pharmacol., 2005, 59(5), 552-563.
205. Kariya, S.; Isozaki, S.; Uchino, K.; Suzuki, T.; Narimatsu, S. Oxidative metabolism of flunarizine and cinnarizine by microsomes from B-lymphoblastoid cell lines expressing human cytochrome P450 enzymes. Biol. Pharm. Bull., 1996, 19(11), 1511-1514.
206. Bohets, H.; Lavrijsen, K.; Hendrickx, J.; van Houdt, J.; van Genechten, V.; Verboven, P.; Meuldermans, W.; Heykants, J. Identification of the cytochrome P450 enzymes involved in the metabolism of cisapride: in vitro studies of potential co-medication interactions. Br. J. Pharmacol., 2000, 129(8), 1655-1667.
207. von Moltke, L.L.; Greenblatt, D.J.; Giancarlo, G.M.; Granda, B.W.; Harmatz, J.S.; Shader, R.I. Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram. Drug Metab. Dispos., 2001, 29(8), 1102-1109.
208. Clarke, T.A.; Waskell, L.A. The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin. Drug Metab. Dispos., 2003, 31(1), 53-59.
209. Tugnait, M.; Hawes, E.M.; McKay, G.; Eichelbaum, M.; Midha, K.K. Characterization of the human hepatic cytochromes P450 involved in the in vitro oxidation of clozapine. Chem. Biol. Interact., 1999, 118(2), 171-189.
210. Griskevicius, L.; Yasar, U.; Sandberg, M.; Hidestrand, M.; Eliasson, E.; Tybring, G.; Hassan, M.; Dahl, M.L. Bioactivation of cyclophosphamide: the role of polymorphic CYP2C enzymes. Eur. J. Clin. Pharmacol., 2003, 59(2), 103-109.
211. Uehleke, H.; Tabarelli, S. N-Hydroxylation of 4,4-diaminodiphenyl- sulfone (dapsone) by liver microsomes and in dogs and humans. Naunyn-Schmeideberg's Arch. Pharmacol., 1973, 278, 55-68.
212. Venkatakrishnan, K.; von Moltke, L.L.; Duan, S.X.; Fleishaker, J.C.; Shader, R.I.; Greenblatt, D.J. Kinetic characterization and identification of the enzymes responsible for the hepatic biotransformation of adinazolam and N-desmethyladinazolam in man. J. Pharm. Pharmacol., 1998, 50(3), 265-274.
213. Barnhart, J.W. The urinary excretion of dextromethorphan and three metabolites in dogs and humans. Toxicol. Appl. Pharmacol., 1980, 55(1), 43-48.
214. Yasumori, T.; Nagata, K.; Yang, S.K.; Chen, L.S.; Murayama, N.; Yamazoe, Y.; Kato, R. Cytochrome P450 mediated metabolism of diazepam in human and rat: involvement of human CYP2C in Ndemethylation in the substrate concentration-dependent manner. Pharmacogenetics, 1993, 3(6), 291-301.
215. Tang, W.; Stearns, R.A.; Wang, R.W.; Chiu, S.H.; Baillie, T.A. Roles of human hepatic cytochrome P450s 2C9 and 3A4 in the metabolic activation of diclofenac. Chem. Res. Toxicol., 1999, 12(2), 192-199.
216. Pearce, R.; Greenway, D.; Parkinson, A. Species differences and interindividual variation in liver microsomal cytochrome P450 2A enzymes: effects on coumarin, dicumarol, and testosterone oxidation. Arch. Biochem. Biophys., 1992, 298(1), 211-225.
217. Sutton, D.; Butler, A.M.; Nadin, L.; Murray, M. Role of CYP3A4 in human hepatic diltiazem N-demethylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolites. J. Pharmacol. Exp. Ther., 1997, 282(1), 294-300.
218. Chou, Y.C.; Chung, Y.T.; Liu, T.Y.; Wang, S.Y.; Chau, G.Y.; Chi, C.W.; Soucek, P.; Krausz, K.W.; Gelboin, H.V.; Lee, C.H.; Ueng, Y.F. The oxidative metabolism of dimemorfan by human cytochrome P450 enzymes. J. Pharm. Sci., 2009, 99(2), 1063-1077.
219. Akutsu, T.; Kobayashi, K.; Sakurada, K.; Ikegaya, H.; Furihata, T.; Chiba, K. Identification of human cytochrome P450 isozymes involved in diphenhydramine N-demethylation. Drug Metab. Dispos., 2007, 35(1), 72-78.
220. 3 antagonists. Drug Metab. Dispos., 1996, 24(5), 602-609.
221. Tiseo, P.J.; Perdomo, C.A.; Friedhoff, L.T. Metabolism and elimination of 14C-donepezil in healthy volunteers: a single-dose study. Br. J. Clin. Pharmacol., 1998, 46(Suppl 1), 19-24.
222. Martens-Lobenhoffer, J.; Banditt, P. Clinical pharmacokinetics of dorzolamide. Clin. Pharmacokinet., 2002, 41(3), 197-205.
223. Evans, D.C.; O'Connor, D.; Lake, B.G.; Evers, R.; Allen, C.; Hargreaves, R. Eletriptan metabolism by human hepatic CYP450 enzymes and transport by human P-glycoprotein. Drug Metab. Dispos., 2003, 31(7), 861-869.
224. Stiborova, M.; Sejbal, J.; Borek-Dohalska, L.; Aimova, D.; Poljakova, J.; Forsterova, K.; Rupertova, M.; Wiesner, J.; Hudecek, J.; Wiessler, M.; Frei, E. The anticancer drug ellipticine forms covalent DNA adducts, mediated by human cytochromes P450, through metabolism to 13-hydroxyellipticine and ellipticine N2-oxide. Cancer Res., 2004, 64(22), 8374-8380.
225. Tougou, K.; Gotou, H.; Ohno, Y.; Nakamura, A. Stereoselective glucuronidation and hydroxylation of etodolac by UGT1A9 and CYP2C9 in man. Xenobiotica, 2004, 34(5), 449-461.
226. Chauret, N.; Yergey, J.A.; Brideau, C.; Friesen, R.W.; Mancini, J.; Riendeau, D.; Silva, J.; Styhler, A.; Trimble, L.A.; Nicoll-Griffith, D.A. In vitro metabolism considerations, including activity testing of metabolites, in the discovery and selection of the COX-2 inhibitor etoricoxib (MK-0663). Bioorg. Med. Chem. Lett., 2001, 11(8), 1059-1062.
227. Scholler-Gyure, M.; Kakuda, T.N.; Raoof, A.; De Smedt, G.; Hoetelmans, R.M. Clinical pharmacokinetics and pharmacodynamics of etravirine. Clin. Pharmacokinet., 2009, 48(9), 561-574.
228. Hesse, L.M.; Venkatakrishnan, K.; von Moltke, L.L.; Shader, R.I.; Greenblatt, D.J. CYP3A4 is the major CYP isoform mediating the in vitro hydroxylation and demethylation of flunitrazepam. Drug Metab. Dispos., 2001, 29(2), 133-140.
229. Margolis, J.M.; O'Donnell, J.P.; Mankowski, D.C.; Ekins, S.; Obach, R.S. R-, S-, and racemic fluoxetine N-demethylation by human cytochrome P450 enzymes. Drug Metab. Dispos., 2000, 28(10), 1187-1191.
230. Tracy, T.S.; Rosenbluth, B.W.; Wrighton, S.A.; Gonzalez, F.J.; Korzekwa, K.R. Role of cytochrome P450 2C9 and an allelic variant in the 4′-hydroxylation of R- and S-flurbiprofen. Biochem. Pharmacol., 1995, 49(9), 1269-1275.
231. Dain, J.G.; Fu, E.; Gorski, J.; Nicoletti, J.; Scallen, T.J. Biotransformation of fluvastatin sodium in humans. Drug Metab. Dispos., 1993, 21(4), 567-572.
232. Toda, T.; Eliasson, E.; Ask, B.; Inotsume, N.; Rane, A. Roles of different CYP enzymes in the formation of specific fluvastatin metabolites by human liver microsomes. Basic Clin. Pharmacol. Toxicol., 2009, 105(5), 327-332.
233. Gilissen, R.A.; Ferrari, L.; Barnaby, R.J.; Kajbaf, M. Human hepatic metabolism of a novel 2-carboxyindole glycine antagonist for stroke: in vitro-in vivo correlations. Xenobiotica, 2000, 30(9), 843-856.
234. Elliot, D.J.; Suharjono; Lewis, B.C.; Gillam, E.M.; Birkett, D.J.; Gross, A.S.; Miners, J.O. Identification of the human cytochromes P450 catalysing the rate-limiting pathways of gliclazide elimination. Br. J. Clin. Pharmacol., 2007, 64(4), 450-457.
235. Badian, M.; Korn, A.; Lehr, K.H.; Malerczyk, V.; Waldhausl, W. Absolute bioavailability of glimepiride (Amaryl) after oral administration. Drug Metabol. Drug Interact., 1994, 11(4), 331-339.
236. Balant, L.; Fabre, J.; Zahnd, G.R. Comparison of the pharmacokinetics of glipizide and glibenclamide in man. Eur. J. Clin. Pharmacol., 1975, 8(1), 63-69.
237. Naritomi, Y.; Terashita, S.; Kagayama, A. Identification and relative contributions of human cytochrome P450 isoforms involved in the metabolism of glibenclamide and lansoprazole: evaluation of an approach based on the in vitro substrate disappearance rate. Xenobiotica, 2004, 34(5), 415-427.
238. Zharikova, O.L.; Fokina, V.M.; Nanovskaya, T.N.; Hill, R.A.; Mattison, D.R.; Hankins, G.D.; Ahmed, M.S. Identification of the major human hepatic and placental enzymes responsible for the biotransformation of glyburide. Biochem. Pharmacol., 2009,
239. Pan, L.P.; De Vriendt, C.; Belpaire, F.M. In vitro characterization of the cytochrome P450 isoenzymes involved in the back oxidation and N-dealkylation of reduced haloperidol. Pharmacogenetics, 1998, 8(5), 383-389.
240. Kharasch, E.D.; Hankins, D.C.; Fenstamaker, K.; Cox, K. Human halothane metabolism, lipid peroxidation, and cytochromes P(450)2A6 and P(450)3A4. Eur. J. Clin. Pharmacol., 2000, 55(11-12), 853-859.
241. Knodell, R.G.; Dubey, R.K.; Wilkinson, G.R.; Guengerich, F.P. Oxidative metabolism of hexobarbital in human liver: relationship to polymorphic S-mephenytoin 4-hydroxylation. J. Pharmacol. Exp. Ther., 1988, 245(3), 845-849.
242. Benetton, S.A.; Borges, V.M.; Chang, T.K.; McErlane, K.M. Role of individual human cytochrome P450 enzymes in the in vitro metabolism of hydromorphone. Xenobiotica, 2004, 34(4), 335-344.
243. Preiss, R.; Schmidt, R.; Baumann, F.; Hanschmann, H.; Hauss, J.; Geissler, F.; Pahlig, H.; Ratzewiss, B. Measurement of 4-hydroxylation of ifosfamide in human liver microsomes using the estimation of free and protein-bound acrolein and codetermination of keto- and carboxyifosfamide. J. Cancer Res. Clin. Oncol., 2002, 128(7), 385-392.
244. 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 mesylate in healthy volunteers. Drug Metab. Dispos., 2005, 33(10), 1503-1512.
245. Nakajima, M.; Inoue, T.; Shimada, N.; Tokudome, S.; Yamamoto, T.; Kuroiwa, Y. Cytochrome P450 2C9 catalyzes indomethacin Odemethylation in human liver microsomes. Drug Metab. Dispos., 1998, 26(3), 261-266.
246. Bourrie, M.; Meunier, V.; Berger, Y.; Fabre, G. Role of cytochrome P450 2C9 in irbesartan oxidation by human liver microsomes. Drug Metab. Dispos., 1999, 27(2), 288-296.
247. Hijazi, Y.; Boulieu, R. Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes. Drug Metab. Dispos., 2002, 30(7), 853-858.
248. Yasar, U.; Annas, A.; Svensson, J.O.; Lazorova, L.; Artursson, P.; Al-Shurbaji, A. Ketobemidone is a substrate for cytochrome P4502C9 and 3A4, but not for P-glycoprotein. Xenobiotica, 2005, 35(8), 785-796.
249. Pearce, R.E.; Rodrigues, A.D.; Goldstein, J.A.; Parkinson, A. Identification of the human P450 enzymes involved in lansoprazole metabolism. J. Pharmacol. Exp. Ther., 1996, 277(2), 805-816.
250. Kalgutkar, A.S.; Nguyen, H.T.; Vaz, A.D.; Doan, A.; Dalvie, D.K.; McLeod, D.G.; Murray, J.C. In vitro metabolism studies on the isoxazole ring scission in the anti-inflammatory agent lefluonomide to its active α-cyanoenol metabolite A771726: mechanistic similarities with the cytochrome P450-catalyzed dehydration of aldoximes. Drug Metab. Dispos., 2003, 31(10), 1240-1250.
251. Albrecht, W.; Unger, A.; Nussler, A.K.; Laufer, S. In vitro metabolism of 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl ] acetic acid (licofelone, ML3000), an inhibitor of cyclooxygenase-1 and -2 and 5-lipoxygenase. Drug Metab. Dispos., 2008, 36(5), 894-903.
252. Wang, J.S.; Backman, J.T.; Taavitsainen, P.; Neuvonen, P.J.; Kivisto, K.T. Involvement of CYP1A2 and CYP3A4 in lidocaine N-deethylation and 3-hydroxylation in humans. Drug Metab. Dispos., 2000, 28(8), 959-965.
253. Monostory, K.; Pascussi, J.M.; Szabo, P.; Temesvari, M.; Kohalmy, K.; Acimovic, J.; Kocjan, D.; Kuzman, D.; Wilzewski, B.; Bernhardt, R.; Kobori, L.; Rozman, D. Drug interaction potential of 2-((3,4-dichlorophenethyl)(propyl) amino)-1-(pyridin-3-yl)ethanol (LK-935), the novel nonstatin-type cholesterollowering agent. Drug Metab. Dispos., 2009, 37(2), 375-385.
254. Ghosal, A.; Gupta, S.; Ramanathan, R.; Yuan, Y.; Lu, X.; Iris Su, A.D.; Alvarez, N.; Zbaida, S.; Chowdhury, S.K.; Alton, K.B. Metabolism of loratadine and further characterization of its in vitro metabolites. Drug Metab. Lett., 2009, 3(3),162-170.
255. Bonnabry, P.; Leemann, T.; Dayer, P. Role of human liver microsomal CYP2C9 in the biotransformation of lornoxicam. Eur. J. Clin. Pharmacol., 1996, 49(4), 305-308.
256. Stearns, R.A.; Chakravarty, P.K.; Chen, R.; Chiu, S.H. Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes. Role of cytochrome P4502C and 3A subfamily members. Drug Metab. Dispos., 1995, 23(2), 207-215.
257. Li, Y.; Slatter, J.G.; Zhang, Z.; Li, Y.; Doss, G.A.; Braun, M.P.; Stearns, R.A.; Dean, D.C.; Baillie, T.A.; Tang, W. In vitro metabolic activation of lumiracoxib in rat and human liver preparations. Drug Metab. Dispos., 2008, 36(2), 469-473.
258. Facciola, G.; Hidestrand, M.; von Bahr, C.; Tybring, G. Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. Eur. J. Clin. Pharmacol., 2001, 56(12), 881-888.
259. Chesne, C.; Guyomard, C.; Guillouzo, A.; Schmid, J.; Ludwig, E.; Sauter, T. Metabolism of meloxicam in human liver involves cytochromes P4502C9 and 3A4. Xenobiotica, 1998, 28(1), 1-13.
260. Ko, J.W.; Desta, Z.; Flockhart, D.A. Human N-demethylation of Smephenytoin by cytochrome P450s 2C9 and 2B6. Drug Metab. Dispos., 1998, 26(8), 775-778.
261. Foster, D.J.; Somogyi, A.A.; Bochner, F. Methadone Ndemethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4. Br. J. Clin. Pharmacol., 1999, 47(4),
262. 403-412.
263. Stormer, E.; Brockmoller, J.; Roots, I.; Schmider, J. Cytochrome P-450 enzymes and FMO3 contribute to the disposition of the antipsychotic drug perazine in vitro. Psychopharmacology (Berl), 2000, 151(4), 312-320.
264. Mayersohn, M.; Guentert, T.W. Clinical pharmacokinetics of the monoamine oxidase-A inhibitor moclobemide. Clin. Pharmacokinet., 1995, 29(5), 292-332.
265. Chiba, M.; Xu, X.; Nishime, J.A.; Balani, S.K.; Lin, J.H. Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans. Drug Metab. Dispos., 1997, 25(9), 1022-1031.
266. Taguchi, K.; Konishi, T.; Nishikawa, H.; Kitamura, S. Identification of human cytochrome P450 isoforms involved in the metabolism of S-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid. Xenobiotica, 1999, 29(9), 899-907.
267. Hirani, V.N.; Raucy, J.L.; Lasker, J.M. Conversion of the HIV protease inhibitor nelfinavir to a bioactive metabolite by human liver CYP2C19. Drug Metab. Dispos., 2004, 32(12), 1462-1467.
268. 14C]naproxen O-demethylase activity in human liver microsomes: evidence for the involvement of cytochrome P4501A2 and P4502C9/10. Drug Metab. Dispos., 1996, 24(1), 126-136.
269. McLeod, J.F. Clinical pharmacokinetics of nateglinide: a rapidlyabsorbed, short-acting insulinotropic agent. Clin. Pharmacokinet., 2004, 43(2), 97-120.
270. Erickson, D.A.; Mather, G.; Trager, W.F.; Levy, R.H.; Keirns, J.J. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P450. Drug Metab. Dispos., 1999, 27(12), 1488-1495.
271. 14C]omeprazole in humans. Drug Metab. Dispos., 1989, 17(1), 69-76.
272. Fischer, V.; Vickers, A.E.; Heitz, F.; Mahadevan, S.; Baldeck, J.P.; Minery, P.; Tynes, R. The polymorphic cytochrome P4502D6 is involved in the metabolism of both 5-hydroxytryptamine antagonists, tropisetron and ondansetron. Drug Metab. Dispos., 1994, 22(2), 269-274.
273. Kobayashi, K.; Nakajima, M.; Oshima, K.; Shimada, N.; Yokoi, T.; Chiba, K. Involvement of CYP2E1 as a low-affinity enzyme in phenacetin O-deethylation in human liver microsomes. Drug Metab. Dispos., 1999, 27(8), 860-865.
274. Hadama, A.; Ieiri, I.; Morita, T.; Kimura, M.; Urae, A.; Irie, S.; Kaneda, T.; Mamiya, K.; Tashiro, N.; Higuchi, S.; Otsubo, K. Phydroxylation of phenobarbital: relationship to S-mephenytoin hydroxylation (CYP2C19) polymorphism. Ther. Drug Monit., 2001, 23(2), 115-118.
275. Rendic, S. Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab. Rev., 2002, 34(1-2), 83-448.
276. Ufer, M.; Svensson, J.O.; Krausz, K.W.; Gelboin, H.V.; Rane, A.; Tybring, G. Identification of cytochromes P450 2C9 and 3A4 as the major catalysts of phenprocoumon hydroxylation in vitro. Eur. J. Clin. Pharmacol., 2004, 60(3), 173-182.
277. Maguire, J.H. Quantitative estimation of catechol/methylcatechol pathways in human phenytoin metabolism. Epilepsia, 1988, 29(6), 753-759.
278. Christensen, M.L.; Meibohm, B.; Capparelli, E.V.; Velasquez-Mieyer, P.; Burghen, G.A.; Tamborlane, W.V. Single- and multiple-dose pharmacokinetics of pioglitazone in adolescents with Type 2 diabetes. J. Clin. Pharmacol., 2005, 45(10), 1137-1144.
279. Leemann, T.; Transon, C.; Dayer, P. Cytochrome P450TB (CYP2C): a major monooxygenase catalyzing diclofenac 4′-hydroxylation in human liver. Life Sci., 1993, 52(1), 29-34.
280. Rehmel, J.L.; Eckstein, J.A.; Farid, N.A.; Heim, J.B.; Kasper, S.C.; Kurihara, A.; Wrighton, S.A.; Ring, B.J. Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes P450. Drug Metab. Dispos., 2006, 34(4), 600-607.
281. Wojcikowski, J.; Pichard-Garcia, L.; Maurel, P.; Daniel, W.A. The metabolism of the piperazine-type phenothiazine neuroleptic perazine by the human cytochrome P-450 isoenzymes. Eur. Neuropsychopharmacol., 2004, 14(3), 199-208.
282. Olesen, O.V.; Linnet, K. Identification of the human cytochrome P450 isoforms mediating in vitro N-dealkylation of perphenazine. Br. J. Clin. Pharmacol., 2000, 50(6), 563-571.
283. Yamazaki, H.; Inoue, K.; Shaw, P.M.; Checovich, W.J.; Guengerich, F.P.; Shimada, T. Different contributions of cytochrome P450 2C19 and 3A4 in the oxidation of omeprazole by human liver microsomes: effects of contents of these two forms in individual human samples. J. Pharmacol. Exp. Ther., 1997, 283(2), 434-442.
284. Wojcikowski, J.; Pichard-Garcia, L.; Maurel, P.; Daniel, W.A. Contribution of human cytochrome P-450 isoforms to the metabolism of the simplest phenothiazine neuroleptic promazine. Br. J. Pharmacol., 2003, 138(8), 1465-1474.
285. Guitton, J.; Buronfosse, T.; Desage, M.; Flinois, J.P.; Perdrix, J.P.; Brazier, J.L.; Beaune, P. Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br. J. Anaesth., 1998, 80(6), 788-795.
286. Slaughter, D.; Takenaga, N.; Lu, P.; Assang, C.; Walsh, D.J.; Arison, B.H.; Cui, D.; Halpin, R.A.; Geer, L.A.; Vyas, K.P.; Baillie, T.A. Metabolism of rofecoxib in vitro using human liver subcellular fractions. Drug Metab. Dispos., 2003, 31(11), 1398-1408.
287. Cox, P.J.; Ryan, D.A.; Hollis, F.J.; Harris, A.M.; Miller, A.K.; Vousden, M.; Cowley, H. Absorption, disposition, and metabolism of rosiglitazone, a potent thiazolidinedione insulin sensitizer, in humans. Drug Metab. Dispos., 2000, 28(7), 772-780.
288. Martin, P.D.; Warwick, M.J.; Dane, A.L.; Hill, S.J.; Giles, P.B.; Phillips, P.J.; Lenz, E. Metabolism, excretion, and pharmacokinetics of rosuvastatin in healthy adult male volunteers. Clin. Ther., 2003, 25(11), 2822-2835.
289. Hidestrand, M.; Oscarson, M.; Salonen, J.S.; Nyman, L.; Pelkonen, O.; Turpeinen, M.; Ingelman-Sundberg, M. CYP2B6 and CYP2C19 as the major enzymes responsible for the metabolism of selegiline, a drug used in the treatment of Parkinson's disease, as revealed from experiments with recombinant enzymes. Drug Metab. Dispos., 2001, 29(11), 1480-1484.
290. Taavitsainen, P.; Anttila, M.; Nyman, L.; Karnani, H.; Salonen, J.S.; Pelkonen, O. Selegiline metabolism and cytochrome P450 enzymes: in vitro study in human liver microsomes. Pharmacol. Toxicol., 2000, 86(5), 215-221.
291. Kumar, G.N.; Dubberke, E.; Rodrigues, A.D.; Roberts, E.; Dennisen, J.F. Identification of cytochromes P450 involved in the human liver microsomal metabolism of the thromboxane A2 inhibitor seratrodast (ABT-001). Drug Metab. Dispos., 1997, 25(1), 110-115.
292. Kobayashi, K.; Ishizuka, T.; Shimada, N.; Yoshimura, Y.; Kamijima, K.; Chiba, K. Sertraline N-demethylation is catalyzed by multiple isoforms of human cytochrome P450 in vitro. Drug Metab. Dispos., 1999, 27(7), 763-766.
293. Warrington, J.S.; Shader, R.I.; von Moltke, L.L.; Greenblatt, D.J. In vitro biotransformation of sildenafil (Viagra): identification of human
294. Winter, H.R.; Unadkat, J.D. Identification of cytochrome P450 and arylamine N-acetyltransferase isoforms involved in sulfadiazine metabolism. Drug Metab. Dispos., 2005, 33(7), 969-976.
295. Miller, J.L.; Trepanier, L.A. Inhibition by atovaquone of CYP2C9-mediated sulphamethoxazole hydroxylamine formation. Eur. J. Clin. Pharmacol., 2002, 58(1), 69-72.
296. He, M.; Rettie, A.E.; Neal, J.; Trager, W.F. Metabolism of sulfinpyrazone sulfide and sulfinpyrazone by human liver microsomes and cDNA-expressed cytochrome P450s. Drug Metab. Dispos., 2001, 29(5), 701-711.
297. Crewe, H.K.; Notley, L.M.; Wunsch, R.M.; Lennard, M.S.; Gillam, E.M. Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4′-hydroxy and Ndesmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab. Dispos., 2002, 30(8), 869-874.
298. Howell, S.R.; Shirley, M.A.; Grese, T.A.; Neel, D.A.; Wells, K.E.; Ulm, E.H. Bexarotene metabolism in rat, dog, and human, synthesis of oxidative metabolites, and in vitro activity at retinoid receptors. Drug Metab. Dispos., 2001, 29(7), 990-998.
299. Vachharajani, N.N.; Yeleswaram, K.; Boulton, D.W. Preclinical pharmacokinetics and metabolism of BMS-214778, a novel melatonin receptor agonist. J. Pharm. Sci., 2003, 92(4), 760-772.
300. Tuvesson, H.; Gunnarsson, P.O.; Seidegard, J. Metabolism of tauromustine in liver and lung microsomes from various species. Xenobiotica, 1999, 29(8), 783-792.
301. Ono, S.; Hatanaka, T.; Miyazawa, S.; Tsutsui, M.; Aoyama, T.; Gonzalez, F.J.; Satoh, T. Human liver microsomal diazepam metabolism using cDNA-expressed cytochrome P450s: role of CYP2B6, 2C19 and the 3A subfamily. Xenobiotica, 1996, 26(11), 1155-1166.
302. Vickers, A.E.; Sinclair, J.R.; Zollinger, M.; Heitz, F.; Glanzel, U.; Johanson, L.; Fischer, V. Multiple cytochrome P450s involved in the metabolism of terbinafine suggest a limited potential for drugdrug interactions. Drug Metab. Dispos., 1999, 27(9), 1029-1038.
303. Watanabe, K.; Yamaori, S.; Funahashi, T.; Kimura, T.; Yamamoto, I. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci., 2007, 80(15), 1415-1419.
304. Lu, J.; Helsby, N.; Palmer, B.D.; Tingle, M.; Baguley, B.C.; Kestell, P.; Ching, L.M. Metabolism of thalidomide in liver microsomes of mice, rabbits, and humans. J. Pharmacol. Exp. Ther., 2004, 310(2), 571-577.
305. Dalvie, D.K.; O'Connell, T.N. Characterization of novel dihydrothienopyridinium and thienopyridinium metabolites of ticlopidine in vitro: role of peroxidases, cytochromes P450, and monoamine oxidases. Drug Metab. Dispos., 2004, 32(1), 49-57.
306. Andersson, S.H.; Lindgren, A.; Postlind, H. Biotransformation of tolterodine, a new muscarinic receptor antagonist, in mice, rats, and dogs. Drug Metab. Dispos., 1998, 26(6), 528-535.
307. Miners, J.O.; Rees, D.L.; Valente, L.; Veronese, M.E.; Birkett, D.J. Human hepatic cytochrome P450 2C9 catalyzes the rate-limiting pathway of torsemide metabolism. J. Pharmacol. Exp. Ther., 1995, 272(3), 1076-1081.
308. Tsuda-Tsukimoto, M.; Ogasawara, Y.; Kume, T. Role of human liver cytochrome P450 2C9 in the metabolism of a novel α4β1/α4β7 dual antagonist, TR-14035. Drug Metab. Pharmacokinet., 2005, 20(2), 127-134.
309. 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(10), 1642-1654.
310. Nakamura, M.; Tanaka, E.; Misawa, S.; Shimada, T.; Imaoka, S.; Funae, Y. Trimethadione metabolism, a useful indicator for assessing hepatic drug-oxidizing capacity. Biochem. Pharmacol., 1994, 47(2), 247-251.
311. Tanaka, E.; Kurata, N.; Yasuhara, H. Involvement of cytochrome P450 2C9, 2E1 and 3A4 in trimethadione N-demethylation in human microsomes. J. Clin. Pharm. Ther., 2003, 28(6), 493-496.
312. Kurata, N.; Nishimura, Y.; Iwase, M.; Fischer, N.E.; Tang, B.K.; Inaba, T.; Yasuhara, H. Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica, 1998, 28(11), 1041-1047.
313. Lai, W.G.; Zahid, N.; Uetrecht, J.P. Metabolism of trimethoprim to a reactive iminoquinone methide by activated human neutrophils and hepatic microsomes. J. Pharmacol. Exp. Ther., 1999, 291(1), 292-299.
314. Yamazaki, H.; Shibata, A.; Suzuki, M.; Nakajima, M.; Shimada, N.; Guengerich, F.P.; Yokoi, T. Oxidation of troglitazone to a quinone-type metabolite catalyzed by cytochrome P450 2C8 and P450 3A4 in human liver microsomes. Drug Metab. Dispos., 1999, 27(11), 1260-1266.
315. He, K.; Talaat, R.E.; Pool, W.F.; Reily, M.D.; Reed, J.E.; Bridges, A.J.; Woolf, T.F. Metabolic activation of troglitazone: identification of a reactive metabolite and mechanisms involved. Drug Metab. Dispos., 2004, 32(6), 639-646.
316. Firkusny, L.; Kroemer, H.K.; Eichelbaum, M. In vitro characterization of cytochrome P450 catalysed metabolism of the antiemetic tropisetron. Biochem. Pharmacol., 1995, 49(12), 1777-1784.
317. Chavez, M.L.; DeKorte, C.J. Valdecoxib: a review. Clin. Ther., 2003, 25(3), 817-851.
318. Sadeque, A.J.; Fisher, M.B.; Korzekwa, K.R.; Gonzalez, F.J.; Rettie, A.E. Human CYP2C9 and CYP2A6 mediate formation of the hepatotoxin 4-ene-valproic acid. J. Pharmacol. Exp. Ther., 1997, 283(2), 698-703.
319. Nakashima, A.; Kawashita, H.; Masuda, N.; Saxer, C.; Niina, M.; Nagae, Y.; Iwasaki, K. Identification of cytochrome P450 forms involved in the 4-hydroxylation of valsartan, a potent and specific angiotensin II receptor antagonist, in human liver microsomes. Xenobiotica, 2005, 35(6), 589-602.
320. Fogelman, S.M.; Schmider, J.; Venkatakrishnan, K.; von Moltke, L.L.; Harmatz, J.S.; Shader, R.I.; Greenblatt, D.J. O- and Ndemethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacology, 1999, 20(5), 480-490.
321. Busse, D.; Cosme, J.; Beaune, P.; Kroemer, H.K.; Eichelbaum, M. Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch. Pharmacol., 1995, 353(1), 116-121.
322. Ghosal, A.; Ramanathan, R.; Yuan, Y.; Hapangama, N.; Chowdhury, S.K.; Kishnani, N.S.; Alton, K.B. Identification of human liver cytochrome P450 enzymes involved in biotransformation of vicriviroc, a CCR5 receptor antagonist. Drug Metab. Dispos., 2007, 35(12), 2186-2195.
323. Hyland, R.; Jones, B.C.; Smith, D.A. Identification of the cytochrome P450 enzymes involved in the N-oxidation of voriconazole. Drug Metab. Dispos., 2003, 31(5), 540-547.
324. Kaminsky, L.S.; Zhang, Z.Y. Human P450 metabolism of warfarin. Pharmacol Ther, 1997, 73(1), 67-74.
325. Savidge, R.D.; Bui, K.H.; Birmingham, B.K.; Morse, J.L.; Spreen, R.C. Metabolism and excretion of zafirlukast in dogs, rats, and mice. Drug Metab. Dispos., 1998, 26(11), 1069-1076.
326. Furuta, S.; Akagawa, N.; Kamada, E.; Hiyama, A.; Kawabata, Y.; Kowata, N.; Inaba, A.; Matthews, A.; Hall, M.; Kurimoto, T. Involvement of CYP2C9 and UGT2B7 in the metabolism of zaltoprofen, a nonsteroidal anti-inflammatory drug, and its lack of clinically significant CYP inhibition potential. Br. J. Clin. Pharmacol., 2002, 54(3), 295-303.
327. Eagling, V.A.; Howe, J.L.; Barry, M.J.; Back, D.J. The metabolism of zidovudine by human liver microsomes in vitro: formation of 3′-amino-3′-deoxythymidine. Biochem. Pharmacol., 1994, 48(2), 267-276.
328. Machinist, J.M.; Mayer, M.D.; Shet, M.S.; Ferrero, J.L.; Rodrigues, A.D. Identification of the human liver cytochrome P450 enzymes involved in the metabolism of zileuton (ABT-077) and its Ndehydroxylated metabolite, Abbott-66193. Drug Metab. Dispos., 1995, 23(10), 1163-1174.
329. Pichard, L.; Gillet, G.; Bonfils, C.; Domergue, J.; Thenot, J.P.; Maurel, P. Oxidative metabolism of zolpidem by human liver cytochrome P450s. Drug Metab. Dispos., 1995, 23(11), 1253-1262.
330. Hagihara, K.; Nishiya, Y.; Kurihara, A.; Kazui, M.; Farid, N.A.; Ikeda, T. Comparison of human cytochrome P450 inhibition by the thienopyridines prasugrel, clopidogrel, and ticlopidine. Drug Metab. Pharmacokinet., 2008, 23(6), 412-420.
331. Yong, W.P.; Kim, T.W.; Undevia, S.D.; Innocenti, F.; Ratain, M.J. R(+)XK469 inhibits hydroxylation of S-warfarin by CYP2C9. Eur. J. Cancer, 2009, 45(11), 1904-1908.
332. Nekvindova, J.; Masek, V.; Veinlichova, A.; Anzenbacherova, E.; Anzenbacher, P.; Zidek, Z.; Holy, A. Inhibition of human liver microsomal cytochrome P450 activities by adefovir and tenofovir. Xenobiotica, 2006, 36(12), 1165-1177.
333. Ohyama, K.; Nakajima, M.; Suzuki, M.; Shimada, N.; Yamazaki, H.; Yokoi, T. Inhibitory effects of amiodarone and its Ndeethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. Br. J. Clin. Pharmacol., 2000, 49(3), 244-253.
334. Di Marco, A.; Marcucci, I.; Chaudhary, A.; Taliani, M.; Laufer, R. Development and validation of a high-throughput radiometric CYP2C9 inhibition assay using tritiated diclofenac. Drug Metab. Dispos., 2005, 33(3), 359-364.
335. Pekthong, D.; Martin, H.; Abadie, C.; Bonet, A.; Heyd, B.; Mantion, G.; Richert, L. Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolide. J. Ethnopharmacol., 2008, 115(3), 432-440.
336. Grimm, S.W.; Dyroff, M.C. Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase. Drug Metab. Dispos., 1997, 25(5), 598-602.
337. Yao, H.T.; Chang, Y.W.; Lan, S.J.; Chen, C.T.; Hsu, J.T.; Yeh, T.K. The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes. Life Sci., 2006, 79(26), 2432-2440.
338. Nicolas, J.M.; Whomsley, R.; Collart, P.; Roba, J. In vitro inhibition of human liver drug metabolizing enzymes by second generation antihistamines. Chem. Biol. Interact., 1999, 123(1), 63-79.
339. McGinnity, D.F.; Berry, A.J.; Kenny, J.R.; Grime, K.; Riley, R.J. Evaluation of time-dependent cytochrome P450 inhibition using cultured human hepatocytes. Drug Metab. Dispos., 2006, 34(8), 1291-1300.
340. Sahi, J.; Stern, R.H.; Milad, M.A.; Rose, K.A.; Gibson, G.; Zheng, X.; Stilgenbauer, L.; Sadagopan, N.; Jolley, S.; Gilbert, D.; LeCluyse, E.L. Effects of avasimibe on cytochrome P450 2C9 expression in vitro and in vivo. Drug Metab. Dispos., 2004, 32(12), 1370-1376.
341. Tassaneeyakul, W.; Guo, L.Q.; Fukuda, K.; Ohta, T.; Yamazoe, Y. Inhibition selectivity of grapefruit juice components on human cytochromes P450. Arch. Biochem. Biophys., 2000, 378(2), 356-363.
342. Fujino, H.; Shimada, S.; Yamada, I.; Hirano, M.; Tsunenari, Y.; Kojima, J. Studies on the interaction between fibrates and statins using human hepatic microsomes. Arzneimittelforschung, 2003, 53(10), 701-707.
343. Lu, C.; Gallegos, R.; Li, P.; Xia, C.Q.; Pusalkar, S.; Uttamsingh, V.; Nix, D.; Miwa, G.T.; Gan, L.S. Investigation of drug-drug interaction potential of bortezomib in vivo in female Sprague-Dawley rats and in vitro in human liver microsomes. Drug Metab. Dispos., 2006, 34(4), 702-708.
344. Zebothsen, I.; Kunze, T.; Clement, B. Inhibitory effects of cytostatically active 6-aminobenzo[c]phenanthridines on cytochrome P450 enzymes in human hepatic microsomes. Basic Clin. Pharmacol. Toxicol., 2006, 99(1), 37-43.
345. McLaughlin, L.A.; Dickmann, L.J.; Wolf, C.R.; Henderson, C.J. Functional expression and comparative characterization of nine murine cytochromes P450 by fluorescent inhibition screening. Drug Metab. Dispos., 2008, 36(7), 1322-1331.
346. Hemeryck, A.; De Vriendt, C.; Belpaire, F.M. Inhibition of CYP2C9 by selective serotonin reuptake inhibitors: in vitro studies with tolbutamide and S-warfarin using human liver microsomes. Eur. J. Clin. Pharmacol., 1999, 54(12), 947-951.
347. Zhao, X.J.; Koyama, E.; Ishizaki, T. An in vitro study on the metabolism and possible drug interactions of rokitamycin, a macrolide antibiotic, using human liver microsomes. Drug Metab. Dispos., 1999, 27(7), 776-785.
348. Walsky, R.L.; Obach, R.S. A comparison of 2-phenyl-2-(1-piperidinyl) propane (PPP), 1,1′,1″-phosphinothioylidynetrisaziridine (thioTEPA), clopidogrel, and ticlopidine as selective inactivators of human cytochrome P450 2B6. Drug Metab. Dispos., 2007, 35(11), 2053-2059.
349. McGinnity, D.F.; Tucker, J.; Trigg, S.; Riley, R.J. Prediction of CYP2C9-mediated drug-drug interactions: a comparison using data from recombinant enzymes and human hepatocytes. Drug Metab. Dispos., 2005, 33(11), 1700-1707.
350. Taavitsainen, P.; Juvonen, R.; Pelkonen, O. In vitro inhibition of cytochrome P450 enzymes in human liver microsomes by a potent CYP2A6 inhibitor, trans-2-phenylcyclopropylamine (tranylcypromine), and its nonamine analog, cyclopropylbenzene. Drug Metab. Dispos., 2001, 29(3), 217-222.
351. Schmider, J.; Greenblatt, D.J.; von Moltke, L.L.; Karsov, D.; Shader, R.I. Inhibition of CYP2C9 by selective serotonin reuptake inhibitors in vitro: studies of phenytoin p-hydroxylation. Br. J. Clin. Pharmacol., 1997, 44(5), 495-498.
352. Oganesian, A.; Shilling, A.D.; Young-Sciame, R.; Tran, J.; Watanyar, A.; Azam, F.; Kao, J.; Leung, L. Desvenlafaxine and venlafaxine exert minimal in vitro inhibition of human cytochrome P450 and P-glycoprotein activities. Psychopharmacol. Bull., 2009, 42(2), 47-63.
353. Hall, M.; Persiani, S.; Cheung, Y.L.; Matthews, A.; Cybulski, Z.R.; Holding, J.D.; Kapil, R.; D'Amato, M.; Makovec, F.; Rovati, L.C. Interaction of dexloxiglumide, a cholecystokinin type-1 receptor antagonist, with human cytochromes P450. Biopharm. Drug Dispos., 2004, 25(4), 163-176.
354. Marks, B.D.; Thompson, D.V.; Goossens, T.A.; Trubetskoy, O.V. High-throughput screening assays for the assessment of CYP2C9*1, CYP2C9*2, and CYP2C9*3 metabolism using fluorogenic Vivid substrates. J. Biomol. Screen., 2004, 9(5), 439-449.
355. Eagling, V.A.; Tjia, J.F.; Back, D.J. Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes. Br. J. Clin. Pharmacol., 1998, 45(2), 107-114.
356. Niwa, T.; Inoue-Yamamoto, S.; Shiraga, T.; Takagi, A. Effect of antifungal drugs on cytochrome P450 (CYP) 1A2, CYP2D6, and CYP2E1 activities in human liver microsomes. Biol. Pharm. Bull., 2005, 28(9), 1813-1816.
357. Nelson, M.H.; Birnbaum, A.K.; Remmel, R.P. Inhibition of phenytoin hydroxylation in human liver microsomes by several selective serotonin re-uptake inhibitors. Epilepsy Res., 2001, 44(1), 71-82.
358. Fujino, H.; Yamada, I.; Shimada, S.; Hirano, M.; Tsunenari, Y.; Kojima, J. Interaction between fibrates and statins??metabolic interactions with gemfibrozil. Drug Metabol. Drug Interact., 2003, 19(3), 161-176.
359. Takahashi, K.; Uejima, E.; Morisaki, T.; Takahashi, K.; Kurokawa, N.; Azuma, J. In vitro inhibitory effects of Kampo medicines on metabolic reactions catalyzed by human liver microsomes. J. Clin. Pharm. Ther., 2003, 28(4), 319-327.
360. Andersson, T.B.; Bredberg, E.; Ericsson, H.; Sjoberg, H. An evaluation of the in vitro metabolism data for predicting the clearance and drug-drug interaction potential of CYP2C9 substrates. Drug Metab. Dispos., 2004, 32(7), 715-721.
361. Ko, J.W.; Sukhova, N.; Thacker, D.; Chen, P.; Flockhart, D.A. Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. Drug Metab. Dispos., 1997, 25(7), 853-862.
362. Liu, K.H.; Kim, M.J.; Jung, W.M.; Kang, W.; Cha, I.J.; Shin, J.G. Lansoprazole enantiomer activates human liver microsomal CYP2C9 catalytic activity in a stereospecific and substrate-specific manner. Drug Metab. Dispos., 2005, 33(2), 209-213.
363. Zhang, J.W.; Liu, Y.; Li, W.; Hao, D.C.; Yang, L. Inhibitory effect of medroxyprogesterone acetate on human liver cytochrome P450 enzymes. Eur. J. Clin. Pharmacol., 2006, 62(7), 497-502.
364. Guo, Z.; Raeissi, S.; White, R.B.; Stevens, J.C. Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab. Dispos., 1997, 25(3), 390-393.
365. O'Reilly, R.A.; Goulart, D.A.; Kunze, K.L.; Neal, J.; Gibaldi, M.; Eddy, A.C.; Trager, W.F. Mechanisms of the stereoselective interaction between miconazole and racemic warfarin in human subjects. Clin. Pharmacol. Ther., 1992, 51(6), 656-667.
366. Brown, H.S.; Galetin, A.; Hallifax, D.; Houston, J.B. Prediction of in vivo drug-drug interactions from in vitro data : factors affecting prototypic drug-drug interactions involving CYP2C9, CYP2D6 and CYP3A4. Clin. Pharmacokinet., 2006, 45(10), 1035-1050.
367. Nakamura, K.; Ariyoshi, N.; Iwatsubo, T.; Fukunaga, Y.; Higuchi, S.; Itoh, K.; Shimada, N.; Nagashima, K.; Yokoi, T.; Yamamoto, K.; Horiuchi, R.; Kamataki, T. Inhibitory effects of nicardipine to cytochrome P450 (CYP) in human liver microsomes. Biol. Pharm. Bull., 2005, 28(5), 882-885.
368. Bapiro, T.E.; Egnell, A.C.; Hasler, J.A.; Masimirembwa, C.M. Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab. Dispos., 2001, 29(1), 30-35.
369. Zhou, Q.; Zhou, S.; Chan, E. Effect of omeprazole on the hydroxylation of warfarin enantiomers in human: In-vitro studies with liver microsomes and cDNA-expressed cytochrome P450 isozymes. Curr. Drug Metab., 2005, 6(5), 399-411.
370. Liu, K.H.; Kim, M.J.; Shon, J.H.; Moon, Y.S.; Seol, S.Y.; Kang, W.; Cha, I.J.; Shin, J.G. Stereoselective inhibition of cytochrome P450 forms by lansoprazole and omeprazole in vitro. Xenobiotica, 2005, 35(1), 27-38.
371. Sahi, J.; Black, C.B.; Hamilton, G.A.; Zheng, X.; Jolley, S.; Rose, K.A.; Gilbert, D.; LeCluyse, E.L.; Sinz, M.W. Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab. Dispos., 2003, 31(4), 439-446.
372. Nagata, M.; Hidaka, M.; Sekiya, H.; Kawano, Y.; Yamasaki, K.; Okumura, M.; Arimori, K. Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats. Drug Metab. Dispos., 2007, 35(2), 302-305.
373. Liu, K.H.; Lee, Y.M.; Shon, J.H.; Kim, M.J.; Lee, S.S.; Yoon, Y.R.; Cha, I.J.; Shin, J.G. Potential of pranlukast and zafirlukast in the inhibition of human liver cytochrome P450 enzymes. Xenobiotica, 2004, 34(5), 429-438.
374. Ring, B.J.; Gillespie, J.S.; Binkley, S.N.; Campanale, K.M.; Wrighton, S.A. The interactions of a selective protein kinase Cβ inhibitor with the human cytochromes P450. Drug Metab. Dispos., 2002, 30(9), 957-961.
375. Beckmann-Knopp, S.; Rietbrock, S.; Weyhenmeyer, R.; Bocker, R.H.; Beckurts, K.T.; Lang, W.; Hunz, M.; Fuhr, U. Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol. Toxicol., 2000, 86(6), 250-256.
376. Prueksaritanont, T.; Gorham, L.M.; Ma, B.; Liu, L.; Yu, X.; Zhao, J.J.; Slaughter, D.E.; Arison, B.H.; Vyas, K.P. In vitro metabolism of simvastatin in humans: identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab. Dispos., 1997, 25(10), 1191-1199.
377. Wen, X.; Wang, J.S.; Backman, J.T.; Laitila, J.; Neuvonen, P.J. Trimethoprim and sulfamethoxazole are selective inhibitors of CYP2C8 and CYP2C9, respectively. Drug Metab. Dispos., 2002, 30(6), 631-635.
378. Donato, M.T.; Jimenez, N.; Castell, J.V.; Gomez-Lechon, M.J. Fluorescence-based assays for screening nine cytochrome P450 (P450) activities in intact cells expressing individual human P450 enzymes. Drug Metab. Dispos., 2004, 32(7), 699-706.
379. Micuda, S.; Mundlova, L.; Anzenbacherova, E.; Anzenbacher, P.; Chladek, J.; Fuksa, L.; Martinkova, J. Inhibitory effects of memantine on human cytochrome P450 activities: prediction of in vivo drug interactions. Eur. J. Clin. Pharmacol., 2004, 60(8), 583-589.
380. He, M.; Kunze, K.L.; Trager, W.F. Inhibition of (S)-warfarin metabolism by sulfinpyrazone and its metabolites. Drug Metab. Dispos., 1995, 23(6), 659-663.
381. Wen, X.; Wang, J.S.; Kivisto, K.T.; Neuvonen, P.J.; Backman, J.T. In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9). Br. J. Clin. Pharmacol., 2001, 52(5), 547-553.
382. Ball, S.E.; Ahern, D.; Scatina, J.; Kao, J. Venlafaxine: in vitro inhibition of CYP2D6 dependent imipramine and desipramine metabolism; comparative studies with selected SSRIs, and effects on human hepatic CYP3A4, CYP2C9 and CYP1A2. Br. J. Clin. Pharmacol., 1997, 43(6), 619-626.
383. Kunze, K.L.; Eddy, A.C.; Gibaldi, M.; Trager, W.F. Metabolic enantiomeric interactions: the inhibition of human (S)-warfarin-7-hydroxylase by (R)-warfarin. Chirality, 1991, 3(1), 24-29.
384. Jeong, S.; Nguyen, P.D.; Desta, Z. Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes: major effect on CYPs 2B6, 2C9, 2C19, and 3A. Antimicrob. Agents Chemother., 2009, 53(2), 541-551.
385. Shader, R.I.; Granda, B.W.; von Moltke, L.L.; Giancarlo, G.M.; Greenblatt, D.J. Inhibition of human cytochrome P450 isoforms in vitro by zafirlukast. Biopharm. Drug Dispos., 1999, 20(8), 385-388.