Development of an in vitro system with human liver microsomes for phenotyping of CYP2C9 genetic polymorphisms with a mechanism-based inactivator

Drug Metabolism and Disposition

Volumn 40, Issue 4, 2012, Pages 836-842

  Flora, Darcy R ^a   Tracy, Timothy S ^b  

^a UNIVERSITY OF MINNESOTA   (United States)

^b University of Kentucky   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMFEBUTAMONE; AMODIAQUINE; BUFURALOL; CHLORZOXAZONE; CYTOCHROME P450 1A2; CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 2E1; CYTOCHROME P450 3A; DEXTROMETHORPHAN; ETHOXYRESORUFIN; FLURBIPROFEN; OMEPRAZOLE; TESTOSTERONE; TIENILIC ACID;

ARTICLE; CONTROLLED STUDY; CYP2C9 GENE; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME INACTIVATION; ENZYME SUBSTRATE; GENE; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; LIVER MICROSOME METABOLISM; PHENOTYPE; PRIORITY JOURNAL;

ARYL HYDROCARBON HYDROXYLASES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INTERACTIONS; ENZYME INHIBITORS; GENOTYPE; HUMANS; MICROSOMES, LIVER; MODELS, BIOLOGICAL; PHARMACEUTICAL PREPARATIONS; PHENOTYPE; POLYMORPHISM, GENETIC; TICRYNAFEN;

EID: 84858408761     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.111.043372     Document Type: Article

References (40)

1. Belghazi M, Jean P, Poli S, Schmitter JM, Mansuy D, and Dansette PM (2001) Use of isotopes and LC-MS-ESI-TOF for mechanistic studies of tienilic acid metabolic activation. Adv Exp Med Biol 500:139-144. (Pubitemid 34106989)
2. Bhasker CR, Miners JO, Coulter S, and Birkett DJ (1997) Allelic and functional variability of cytochrome P4502C9. Pharmacogenetics 7:51-58. (Pubitemid 27153319)
3. Bjornsson TD, Callaghan JT, Einolf HJ, Fischer V, Gan L, Grimm S, Kao J, King SP, Miwa G, Ni L, et al. (2003) The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. Drug Metab Dispos 31:815-832. (Pubitemid 36759050)
4. Chittur SV and Tracy TS (1997) Rapid and sensitive high-performance liquid chromatographic assay for 6-hydroxychlorzoxazone and chlorzoxazone in liver microsomes. J Chromatogr B Biomed Sci Appl 693:479-483. (Pubitemid 27250312)
5. Coles R and Kharasch ED (2008) Stereoselective metabolism of bupropion by cytochrome P4502B6 (CYP2B6) and human liver microsomes. Pharm Res 25:1405-1411.
6. Coller JK, Krebsfaenger N, Klein K, Endrizzi K, Wolbold R, Lang T, Nüssler A, Neuhaus P, Zanger UM, Eichelbaum M, et al. (2002) The influence of CYP2B6, CYP2C9 and CYP2D6 genotypes on the formation of the potent antioestrogen Z-4-hydroxy-tamoxifen in human liver. Br J Clin Pharmacol 54:157-167. (Pubitemid 35024939)
7. Crespi CL, Chang TK, and Waxman DJ (2006) CYP2D6-dependent bufuralol 1&prime-hydroxylation assayed by reverse-phase ion-pair high-performance liquid chromatography with fluorescence detection. Methods Mol Biol 320:121-125.
8. Dansette PM, Amar C, Valadon P, Pons C, Beaune PH, and Mansuy D (1991) Hydroxylation and formation of electrophilic metabolites of tienilic acid and its isomer by human liver microsomes: catalysis by a cytochrome P450 IIC different from that responsible for mephenytoin hydroxylation. Biochem Pharmacol 41:553-560.
9. Gotoh O (1992) Substrate recognition sites in cytochrome P450 family 2 (CYP2) proteins inferred from comparative analyses of amino acid and coding nucleotide sequences. J Biol Chem 267:83-90.
10. Haining RL, Hunter AP, Veronese ME, Trager WF, and Rettie AE (1996) Allelic variants of human cytochrome P450 2C9: baculovirus-mediated expression, purification, structural characterization, substrate stereoselectivity, and prochiral selectivity of the wild-type and I359L mutant forms. Arch Biochem Biophys 333:447-458. (Pubitemid 26304913)
11. Hollenberg PF, Kent UM, and Bumpus NN (2008) Mechanism-based inactivation of human cytochromes P450s: experimental characterization, reactive intermediates, and clinical implications. Chem Res Toxicol 21:189-205. (Pubitemid 351219719)
12. Homberg JC, Andre C, and Abuaf N (1984) A new anti-liver-kidney microsome antibody (anti-LKM2) in tienilic acid-induced hepatitis. Clin Exp Immunol 55:561-570. (Pubitemid 14185814)
13. Hummel MA, Locuson CW, Gannett PM, Rock DA, Mosher CM, Rettie AE, and Tracy TS (2005) CYP2C9 genotype-dependent effects on in vitro drug-drug interactions: switching of benzbromarone effect from inhibition to activation in the CYP2C9.3 variant. Mol Pharmacol 68:644-651. (Pubitemid 41206018)
14. Hutzler JM, Balogh LM, Zientek M, Kumar V, and Tracy TS (2009) Mechanism-based inactivation of cytochrome P450 2C9 by tienilic acid and (±)-suprofen: a comparison of kinetics and probe substrate selection. Drug Metab Dispos 37:59-65.
15. Koenigs LL, Peter RM, Hunter AP, Haining RL, Rettie AE, Friedberg T, Pritchard MP, Shou M, Rushmore TH, and Trager WF (1999) Electrospray ionization mass spectrometric analysis of intact cytochrome P450: identification of tienilic acid adducts to P450 2C9. Biochemistry 38:2312-2319.
16. Kumar V, Brundage RC, Oetting WS, Leppik IE, and Tracy TS (2008) Differential genotype dependent inhibition of CYP2C9 in humans. Drug Metab Dispos 36:1242-1248. (Pubitemid 351929306)
17. Kumar V, Wahlstrom JL, Rock DA, Warren CJ, Gorman LA, and Tracy TS (2006) CYP2C9 inhibition: impact of probe selection and pharmacogenetics on in vitro inhibition profiles. Drug Metab Dispos 34:1966-1975. (Pubitemid 44837757)
18. Lecoeur S, Bonierbale E, Challine D, Gautier JC, Valadon P, Dansette PM, Catinot R, Ballet F, Mansuy D, and Beaune PH (1994) Specificity of in vitro covalent binding of tienilic acid metabolites to human liver microsomes in relationship to the type of hepatotoxicity: comparison with two directly hepatotoxic drugs. Chem Res Toxicol 7:434-442. (Pubitemid 24150106)
19. Lee CR, Goldstein JA, and Pieper JA (2002) Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics 12:251-263. (Pubitemid 34596790)
20. Li XQ, Andersson TB, Ahlström M, and Weidolf L (2004) Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 32:821-827. (Pubitemid 38955611)
21. López-García MP, Dansette PM, and Coloma J (2005) Kinetics of tienilic acid bioactivation and functional generation of drug-protein adducts in intact rat hepatocytes. Biochem Pharmacol 70:1870-1882. (Pubitemid 41612018)
22. López-Garcia MP, Dansette PM, and Mansuy Dand Mansuy D (1994) Thiophene derivatives as new mechanism-based inhibitors of cytochromes P-450: inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic acid. Biochemistry 33:166-175. (Pubitemid 24046510)
23. Mansuy D, Dansette PM, Foures C, Jaouen M, Moinet G, and Bayer N (1984) Metabolic hydroxylation of the thiophene ring: isolation of 5-hydroxy-tienilic acid as the major urinary metabolite of tienilic acid in man and rat. Biochem Pharmacol 33:1429-1435. (Pubitemid 14105014)
24. McGinnity DF, Berry AJ, Kenny JR, Grime K, and Riley RJ (2006) Evaluation of timedependent cytochrome P450 inhibition using cultured human hepatocytes. Drug Metab Dispos 34:1291-1300. (Pubitemid 44079869)
25. Nishiya T, Mori K, Hattori C, Kai K, Kataoka H, Masubuchi N, Jindo T, and Manabe S (2008) The crucial protective role of glutathione against tienilic acid hepatotoxicity in rats. Toxicol Appl Pharmacol 232:280-291.
26. Rendic S (2002) Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev 34:83-448.
27. Sano E, Li W, Yuki H, Liu X, Furihata T, Kobayashi K, Chiba K, Neya S, and Hoshino T (2010) Mechanism of the decrease in catalytic activity of human cytochrome P450 2C9 polymorphic variants investigated by computational analysis. J Comput Chem 31:2746-2758.
28. Shimada T, Yamazaki H, Mimura M, Inui Y, and Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423. (Pubitemid 24229655)
29. Steward DJ, Haining RL, Henne KR, Davis G, Rushmore TH, Trager WF, and Rettie AE (1997) Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics 7:361-367. (Pubitemid 27427545)
30. Subramanian M, Low M, Locuson CW, and Tracy TS (2009) CYP2D6-CYP2C9 protein-protein interactions and isoform-selective effects on substrate binding and catalysis. Drug Metab Dispos 37:1682-1689.
31. Subramanian M, Tam H, Zheng H, and Tracy TS (2010) CYP2C9-CYP3A4 protein-protein interactions: role of the hydrophobic N terminus. Drug Metab Dispos 38:1003-1009.
32. Sullivan-Klose TH, Ghanayem BI, Bell DA, Zhang ZY, Kaminsky LS, Shenfield GM, Miners JO, Birkett DJ, and Goldstein JA (1996) The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 6:341-349. (Pubitemid 26288624)
33. Takanashi K, Tainaka H, Kobayashi K, Yasumori T, Hosakawa M, and Chiba K (2000) CYP2C9 Ile359 and Leu359 variants: enzyme kinetic study with seven substrates. Pharmacogenetics 10:95-104. (Pubitemid 30193071)
34. Tracy TS, Hutzler JM, Haining RL, Rettie AE, Hummel MA, and Dickmann LJ (2002) Polymorphic variants (CYP2C9*3 and CYP2C9*5) and the F114L active site mutation of CYP2C9: effect on atypical kinetic metabolism profiles. Drug Metab Dispos 30:385-390. (Pubitemid 34263822)
35. Tracy TS, Wirthwein DP, and Hall SD (1993) Metabolic inversion of (R)-ibuprofen: formation of ibuprofenyl-coenzyme A. Drug Metab Dispos 21:114-120. (Pubitemid 23052230)
36. Walsky RL, Astuccio AV, and Obach RS (2006) Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol 46:1426-1438. (Pubitemid 44704203)
37. Wang B, Wang J, Huang SQ, Su HH, and Zhou SF (2009) Genetic polymorphism of the human cytochrome P450 2C9 gene and its clinical significance. Curr Drug Metab 10:781-834.
38. Wei L, Locuson CW, and Tracy TS (2007) Polymorphic variants of CYP2C9: mechanisms involved in reduced catalytic activity. Mol Pharmacol 72:1280-1288. (Pubitemid 350012601)
39. Wester MR, Yano JK, Schoch GA, Yang C, Griffin KJ, Stout CD, and Johnson EF (2004) The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0- Å resolution. J Biol Chem 279:35630-35637. (Pubitemid 39100565)
40. Yu A and Haining RL (2001) Comparative contribution to dextromethorphan metabolism by cytochrome P450 isoforms in vitro: can dextromethorphan be used as a dual probe for both CTP2D6 and CYP3A activities? Drug Metab Dispos 29:1514-1520. (Pubitemid 33000701)