CYP2C9 genotype as a predictor of drug disposition in humans

Methods and Findings in Experimental and Clinical Pharmacology

Volumn 26, Issue 6, 2004, Pages 463-472

  Lee, Craig R ^a  

^a UNIVERSITY OF NORTH CAROLINA   (United States)

Author keywords

CYP2C9; Drug disposition; Pharmacogenetics; Polymorphism

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; CANDESARTAN; CELECOXIB; CYTOCHROME P450 2C9; DICLOFENAC; FLURBIPROFEN; GLIBENCLAMIDE; GLIMEPIRIDE; IRBESARTAN; LOSARTAN; NATEGLINIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PHENYTOIN; SULFONYLUREA; TOLBUTAMIDE; WARFARIN;

ALLELE; ASIAN; CLINICAL TRIAL; DRUG DISPOSITION; ETHNOLOGY; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; METABOLISM; NEGRO; PHARMACOGENETICS; REVIEW;

ARYL HYDROCARBON HYDROXYLASES; GENOTYPE; HUMANS; PHARMACEUTICAL PREPARATIONS; PREDICTIVE VALUE OF TESTS; TISSUE DISTRIBUTION;

EID: 4143069198     PISSN: 03790355     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (69)

1. Rendic, S., Di Carlo, F.J. Human cytochrome P450 enzymes: A status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 1997, 29: 413-580.
2. Parkinson, A. Biotransformation of xenobiotics. In: Casarett & Doull's Toxicology. Klaassen, C.D. (Ed.). 5th Ed. McGraw-Hill 1996, 113-86.
3. Rettie, A.E., Korzekwa, K.R., Kunze, K.L. et al. Hydroxylation of warfarin by human cDNA-expressed cytochrome P450: A role for P4502C9 in the etiology of (S)-warfarin drug interactions. Chem Res Toxicol 1992, 5: 54-9.
4. 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: 1401-3.
5. Stearns, R.A., Chakravarty, P.K., Chen, R., Chiu, S.H.L. Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes. Drug Metab Dispos 1995, 23: 207-15.
6. Miners, J.O., Birkett, D.J. The use of tolbutamide as a substrate probe for human hepatic P4502C9. Methods Enzymol 1996, 272: 139-45.
7. Tracy, T.S., Rosenbluth, B.W., Wrighton, S.A., Gonzalez, F.J., Korzekwa, K.R. Role of cytochrome P4502C9 and an allelic variant in the 4'-hydroxylation of (R)- and (S)-flurbiprofen. Biochem Pharmacol 1995, 49: 1269-75.
8. Miners, J.O., Birkett, D.J. Cytochrome P4502C9: An enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 1998, 45: 525-38.
9. Meehan, R.R., Gosden, J.R., Rout, D. et al. Human cytochrome P450 PB-1: A multigene family involved in mephenytoin and steroid oxidations that maps to chromosome 10. Am J Hum Genet 1988, 42: 26-37.
10. Goldstein, J.A., de Morais, S.M.F. Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics 1994, 4: 285-99.
11. Lee, C.R., Goldstein, J.A., Pieper, J.A. Cytochrome P450 2C9 polymorphisms: A comprehensive review of the in vitro and human data. Pharmacogenetics 2002, 12: 251-63.
12. Goldstein, J.A. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol 2001, 52: 349-55.
13. Xie, H.G., Prasad, H.C., Kim, R.B., Stein, C.M. CYP2C9 allelic variants: Ethnic distribution and functional significance. Adv Drug Deliv Rev 2002, 54: 1257-70.
14. Takahashi, H., Echizen, H. Pharmacogenetics of warfarin elimination and its clinical implications. Clin Pharmacokinet 2001, 40: 587-603.
15. Stubbins, M.J., Harries, L.W., Smith, G., Tarbit, M.H., Wolf, C.R. Genetic analysis of the human cytochrome P450 CYP2C9 locus. Pharmacogenetics 1996, 6: 429-39.
16. 359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 1996, 6: 341-9.
17. Bhasker, C.R., Miners, J.O., Coulter, S., Birkett, D.J. Allelic and functional variability of cytochrome P4502C9. Pharmacogenetics 1997, 7: 51-8.
18. Imai, J., Ieiri, I., Mamiya, K., Miyahara, S., Furuumi, H., Nanba, E. Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients: Genetic analysis of the CYP2C9 locus. Pharmacogenetics 2000, 10: 85-9.
19. Dickmann, L.J., Rettie, A.E., Kneller, M.B. et al. Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5) expressed among African-Americans. Mol Pharmacol 2001, 60: 382-7.
20. Kidd, R.S., Curry, T.B., Gallagher, S., Edeki, T., Blaisdell, J., Goldstein, J.A. Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics 2001, 11: 803-8.
21. Leung, A.Y.H., Chow, H.C.H., Kwong, Y.L. et al. Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients. Blood 2001, 98: 2584-7.
22. Rettie, A.E., Tai, G., Veenstra, D.L. et al. CYP2C9 exon 4 mutations and warfarin dose phenotype in Asians. Blood 2003, 101: 2896-7.
23. Shintani, M., Ieiri, I., Inoue, K. et al. Genetic polymorphisms and functional characterization of the 5'-flanking region of the human CYP2C9 gene: In vitro and in vivo studies. Clin Pharmacol Ther 2001, 70: 175-82.
24. Gaikovitch, E.A., Cascorbi, I., Mrozikiewicz, P.M. et al. Polymorphisms of drug-metabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2, and of P-glycoprotein in a Russian population. Eur J Clin Pharmacol 2003, 59: 303-12.
25. Adithan, C., Gerard, N., Vasu, S., Balakrishnan, R., Shashindran, C.H., Krishnamoorthy, R. Allele and genotype frequency of CYP2C9 in Tamilnadu population. Eur J Clin Pharmacol 2003, 59: 707-9.
26. Yasar, U., Aklillu, E., Canaparo, R. et al. Analysis of CYP2C9*5 in Caucasian, Oriental and Black-African populations. Eur J Clin Pharmacol 2002, 58: 555-8.
27. 359 variants: Enzyme kinetic study with seven substrates. Pharmacogenetics 2000, 10: 95-104.
28. Ieiri, I., Tainaka, H., Morita, T. et al. Catalytic activity of three variants (Ile, Leu, and Thr) at amino acid residue 359 in human CYP2C9 gene and simultaneous detection using single-strand conformation polymorphism analysis. Ther Drug Monit 2000, 22: 237-44.
29. Gotoh, O. Substrate recognition sites in cytochrome P450 family 2 (CYP2) proteins inferred from comparative analyses of amino acid and coding nucleotide sequences. J Biol Chem 1992, 267: 83-90.
30. Crespi, C.L., Miller, V.P. The R144C change in CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH: Cytochrome P450 oxidoreductase. Pharmacogenetics 1997, 7: 203-10.
31. Aithal, G.P., Day, C.P., Kesteven, P.J.L., Daly, A.K. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999, 353: 717-9.
32. Taube, J., Halsall, D., Baglin, T. Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood 2000, 96: 1816-9.
33. Margaglione, M., Colaizzo, D., Andrea, G.D. et al. Genetic modulation of oral anticoagulation with warfarin. Thromb Haemost 2000, 84: 775-8.
34. Loebstein, R., Yonath, H., Peleg, D. et al. Interindividual variability in sensitivity to warfarin - nature or nurture? Clin Pharmacol Ther 2001, 70: 159-64.
35. Higashi, M.K., Veenstra, D.L., Kondo, L.M. et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 2002, 287: 1690-8.
36. Scordo, M.G., Pengo, V., Spina, E., Dahl, M.L., Gusella, M., Padrini, R. Influence of CYP2C9 and CYP2CI9 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Clin Pharmacol Ther 2002, 72: 702-10.
37. Linder, M.W., Looney, S., Adams, J.E. et al. Warfarin dose adjustments based on CYP2C9 genetic polymorphisms. J Thromb Thrombolysis 2002, 14: 227-32.
38. Takahashi, H., Wilkinson, G.R., Caraco, Y. et al. Population differences in S-warfarin metabolism between CYP2C9 genotype-matched Caucasian and Japanese patients. Clin Pharmacol Ther 2003, 73: 253-63.
39. Kamali, F., Khan, T.I., King, B.P. et al. Contribution of age, body size, and CYP2C9 genotype to anticoagulant response to warfarin. Clin Pharmacol Ther 2004, 75: 204-12.
40. Peyvandi, F., Spreafico, M., Siboni, S.M., Moia, M., Mannucci, P.M. CYP2C9 genotypes and dose requirements during the induction phase of oral anticoagulant therapy. Clin Pharmacol Ther 2004, 75: 198-203.
41. Hermida, J., Zarza, J., Alberca, I. et al. Differential effects of 2C9*3 and 2C9*2 variants of cytochrome P-450 CYP2C9 on sensitivity to acenocoumarol. Blood 2002, 99: 4237-9.
42. Thijssen, H.H.W., Ritzen, B. Acenocoumarol pharmacokinetics in relation to cytochrome P450 2C9 genotype. Clin Pharmacol Ther 2003, 74: 61-8.
43. Aynacioglu, A.S., Brockmoller, J., Bauer, S. et al. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br J Clin Pharmacol 1999, 48: 409-15.
44. Kerb, R., Aynacioglu, A.S., Brockmoller, J. et al. The predictive value of MDRI, CYP2C9, and CYP2C19 polymorphisms for phenytoin plasma levels. Pharmacogenomics J 2001, 1: 204-10.
45. Caraco, Y., Muszkat, M., Wood, A.J.J. Phenytoin metabolic ratio: A putative marker of CYP2C9 activity in vivo. Pharmacogenetics 2001, 11: 587-96.
46. van der Weide, J., Steijns, L.S., van Weelden, M.J., de Haan, K. The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics 2001, 11: 287-91.
47. Kirchheiner, J., Bauer, S., Meineke, I. et al. Impact of CYP2C9 and CYP2CI9 polymorphisms on tolbutamide kinetics and the insulin and glucose response in healthy volunteers. Pharmacogenetics 2002, 12: 101-9.
48. Kirchheiner, J., Meineke, I., Muller, G. et al. Influence of CYP2C9 and CYP2D6 polymorphisms on the pharmacokinetics of nateglinide in genotyped healthy volunteers. Clin Pharmacokinet 2004, 43: 267-78.
49. Lee, C.R., Pieper, J.A., Hinderliter, A.L., Blaisdell, J.A., Goldstein, J.A. Evaluation of cytochrome P4502C9 metabolic activity with tolbutamide in CYP2C9*1 heterozygotes. Clin Pharmacol Ther 2002, 72: 562-71.
50. Shon, J.H., Yoon, Y.R., Kim, K.A. et al. Effects of CYP2C19 and CYP2C9 genetic polymorphisms on the disposition of and blood glucose lowering response to tolbutamide in humans. Pharmacogenetics 2002, 12: 111-9.
51. Kidd, R.S., Straughn, A.B., Meyer, M.C., Blaisdell, J., Goldstein, J.A., Dalton, J.T. Pharmacokinetics of chlorpheniramine phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics 1999, 9: 71-80.
52. Kirchheiner, J., Brockmoller, J., Meineke, I. et al. Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers. Clin Pharmacol Ther 2002, 71: 286-96.
53. Niemi, M., Cascorbi, I., Timm, R., Kroemer, H.K., Neuvonen, P.J., Kivisto, K.T. Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clin Pharmacol Ther 2002, 72: 326-32.
54. McCrea, J.B., Cribb, A., Rushmore, T. et al. Phenotypic and genotypic investigations of a healthy volunteer deficient in the conversion of losartan to its active metabolite E-3174. Clin Pharmacol Ther 1999, 65: 348-52.
55. Yasar, U., Forslund-Bergengren, C., Tybring, G. et al. Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin Pharmacol Ther 2002, 71: 89-98.
56. Lee, C.R., Pieper, J.A., Hinderliter, A.L., Blaisdell, J.A., Goldstein, J.A. Losartan and E3174 pharmacokinetics in cytochrome P450 2C9*1/ *1, */1*/2, and *1/*3 individuals. Pharmacotherapy 2003, 23: 720-5.
57. Sekino, K., Kubota, T., Okada, Y. et al. Effect of the single CYP2C9*3 allele on pharmacokinetics and pharmacodynamics of losartan in healthy Japanese subjects. Eur J Clin Pharmacol 2003, 59: 589-92.
58. Uchida, S., Wantanabe, H., Nishio, S. et al. Altered pharmacokinetics and excessive hypotensive effect of condesartan in a patient with the CYP2C9*1/*3 genotype. Clin Pharmacol Ther 2003, 74: 505-8.
59. Hallberg. P., Karlsson, J., Kurland, L. et al. The CYP2C9 genotype predicts the blood pressure response to irbesartan: Results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial. J Hypertens 2002, 20: 2089-93.
60. Shimamoto, J., leiri, I., Urae, A. et al. Lack of differences in diclofenac (a substrate for CYP2C9) pharmacokinetics in healthy volunteers with respect to the single CYP2C9*3 allele. Eur J Clin Pharmacol 2000, 56: 65-8.
61. Morin, S., Loriot, M.A., Poirier, J.M. et al. Is diclofenac a valuable CYP2C9 probe in humans? Eur J Clin Pharmacol 2001, 56: 793-7.
62. Yasar, U., Eliasson, E., Forslund-Bergengren, C. et al. The role of CYP2C9 genotype in the metabolism of diclofenac in vivo and in vitro. Eur J Clin Pharmacol 2001, 57: 729-35.
63. Lee, C.R., Pieper, J.A., Frye, R.F., Hinderliter, A.L., Blaisdell, J.A., Goldstein, J.A. Differences in flurbiprofen pharmacokinetics between CYP2C9*1/*1, *1/*2, and *1/*3 genotypes. Eur J Clin Pharmacol 2003, 58: 791-4.
64. Kirchheiner, J., Meineke, I., Freytag, G., Meisel, C., Roots, I., Brockmoller, J. Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. Clin Pharmacol Ther 2002, 72: 62-75.
65. Brenner, S.S., Herrlinger, C., Dilger, K. et al. Influence of age and cytochrome P450 2C9 genotype on the steady-state disposition of diclofenac and celecoxib. Clin Pharmacokinet 2003, 42: 283-92.
66. Kirchheiner, J., Stormer, E., Meisel, C., Steinbach, N., Roots, I., Brockmoller, J. Influence of CYP2C9 genetic polymorphisms on pharmacokinetics of celecoxib and its metabolites. Pharmacogenetics 2003, 13: 473-80.
67. Martinez, C., Blanco, G., Ladero, J.M. et al. Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use. Br J Pharmacol 2004, 141: 205-8.
68. Kirchheiner, J., Kudlicz, D., Meisel, C. et al. Influence of CYP2C9 polymorphisms on the pharmacokinetics and cholesterol-lowering activity of (-)-3S,5R-fluvastatin and (+)-3R,5S-fluvastatin in healthy volunteers. Clin Pharmacol Ther 2003, 74: 186-94.
69. Llerena, A., Dorado, P., Berecz, R., Gonzalez, A.P., Penas-Lledo, E.M. Effect of CYP2D6 and CYP2C9 genotype on fluoxetine and norfluoxetine plasma concentrations during steady-state conditions. Eur J Clin Pharmacol 2004, 59: 869-73.