Role of Human Liver Cytochrome P450 2C9 in the Metabolism of a Novel α4β1/α4β7 Dual Antagonist, TR-14035

Drug Metabolism And Pharmacokinetics

Volumn 20, Issue 2, 2005, Pages 127-134

  Tsuda Tsukimoto, Minoru ^a   Ogasawara, Yuko ^a   Kume, Toshiyuki ^a  

^a MITSUBISHI TANABE PHARMA CORPORATION   (Japan)

Author keywords

CYP2C9; genetic polymorphism; luiman liver microsome; metabolism; 4 1 4 7 antagonist

Indexed keywords

CYP2C9 PROTEIN, HUMAN; DRUG DERIVATIVE; INTEGRIN; INTEGRIN ALPHA4BETA7; ISOENZYME; N (2,6 DICHLOROBENZOYL) 4 (2',6' BISMETHOXYPHENYL)PHENYLALANINE; N-(2,6-DICHLOROBENZOYL)-4-(2',6'-BISMETHOXYPHENYL)PHENYLALANINE; PHENYLALANINE; RECOMBINANT PROTEIN; UNSPECIFIC MONOOXYGENASE; VERY LATE ACTIVATION ANTIGEN 4;

ARTICLE; DRUG ANTAGONISM; ENZYMOLOGY; GENETIC POLYMORPHISM; GENETICS; HUMAN; IN VITRO STUDY; LIVER MICROSOME; METABOLISM; PHYSIOLOGY;

ARYL HYDROCARBON HYDROXYLASES; HUMANS; INTEGRIN ALPHA4BETA1; INTEGRINS; ISOENZYMES; MICROSOMES, LIVER; PHENYLALANINE; POLYMORPHISM, GENETIC; RECOMBINANT PROTEINS;

EID: 21444435755     PISSN: 13474367     EISSN: 18800920     Source Type: Journal    
DOI: 10.2133/dmpk.20.127     Document Type: Article

References (24)

1. Sircar, I., Gudmundsson, K. S., Martin, R., Liang, J., Nomura, S., Jayakumar, H., Teegarden, B. R., Nowlin, D. M., Cardarelli, P. M., Mah, J. R., Connell, S., Griffith, R. C. and Lazarides, E.: Synthesis and SAR of N-benzoyl-L-biphenylalanine derivatives: Discovery of TR-14035, a dual a4β7/a4β1 integrin antagonist. Bioorg. Med. Chem., 10: 2051-2066 (2002).
2. Tang, C., Shou, M., Rushmore, T. H., Mei, Q., Sandhu, P., Woolf, E. J., Rose, M. J., Gelmann, A., Greenberg, H. E., De Lepeleire, I., Van Hecken, A., De Schepper, P. J., Ebel, D. L., Schwartz, J. I. and Rodrigues, A. D.: In vitro metabolism of celecoxib, a cyclooxygenase-2 inhibitor, by allelic variant forms of human liver microsomal cytochrome P450 2C9: correlation with CYP2C9 genotype and in-vivo pharmacokinetics. Pharmacogenetics, 11: 223-235 (2001).
3. Lee, C. R., Goldstein, J. A. and Pieper, J. A.: Cytochrome P450 2C9 polymorphism: a comprehensive review of the in-vitro and human data. Pharmacogenetics, 12: 251-263 (2002).
4. Iida, I., Miyata, A., Arai, M., Hirota, M., Akimoto, M., Higuchi, S., Kobayashi, K. and Chiba, K.: Catalytic roles of CYP2C9 and its variants (CYP2C9*2 and CYP2C9*3) in lornoxicam 5'-hydroxylation. Drug. Metab. Dispos., 32: 7-9 (2004).
5. Takanashi, K., Tainaka, H., Kobayashi, K., Yasumori, T., Hosokawa, M. and Chiba, K.: CYP2C9 Ile359 and Leu359 variants: enzyme kinetic study with seven substrates. Pharmacogenetics, 10: 95-104 (2000).
6. Newton, D. J., Wang, R. W. and Lu, A. Y. H.: Cytochrome P450 inhibitors. Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug. Metab. Dispos., 23: 154-158 (1995).
7. Ono, S., Hatanaka, T., Hotta, H., Satou, T., Gonzalez, F. J. and Tsutsui, M.: Specificity of substrate and inhibitor probes for cytochrome P450s: Evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. Xenobiotica, 26: 681-694 (1996).
8. Bourrié, M., Meunier, V., Berger, Y. and Fabre, G.: Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes. J. Pharmacol. Exp. Ther., 277: 321-332 (1996).
9. Ko, J.-W., Sukhova, N., Thacker, D., Chen, P. and Flockhart, D. A.: Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. Drug. Metab. Dispos., 25: 853-862 (1997).
10. Yamaoka, K., Tanigawara, Y., Nakagawa, T. and Uno, T.: A pharmacokinetics analysis program (MULTI) for microcomputer. J. Pharmacobio-Dyn., 4: 879-885 (1981).
11. Shimada, T., Yamazaki, H., Mimura, M., Inui, Y. and Guengerich, F. P.: 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 (1994).
12. Caraco, Y., Muszkat, M. and Wood, A. J. J.: Phenytoin metabolic ratio: a putative marker of CYP2C9 activity in vivo. Pharmacogenetics, 11: 587-596 (2001).
13. van der Weide, J., Steijns, L. S. W., van Weelden, M. J. M. and de Haan, K.: The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics, 11: 287-291 (2001).
14. Chang, T. K. H., Yu, L., Goldstein, J. A. and Waxman, D. J.: Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Pharmacogenetics, 7: 211-221 (1997).
15. Steward, D. J., Haining, R. L., Henne, K. R., Davis, G., Rushmore, T. H., Trager, W. F. and Rettie, A. E.: Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics, 7: 361-367 (1997).
16. Takahashi, H., Kashima, T., Nomoto, S., Iwade, K., Tainaka, H., Shimizu, T., Nomizo, Y., Muramoto, N., Kimura, S. and Echizen, H.: Comparisons between in-vitro and in-vivo metabolism of (S)-warfarin: catalytic activities of cDNA-expressed CYP2C9, its Leu359 variant and their mixture versus unbound clearance in patients with the corresponding CYP2C9 genotypes. Pharmacogenetics, 8: 365-373 (1998).
17. Kidd, R. S., Straughn, A. B., Meyer, M. C., Blaisdell, J., Goldstein, J. A. and Dalton, J. T.: Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics, 9: 71-80 (1999).
18. Yasar, U., Forslund-Bergengren, C., Tybring, G., Dorado, P., Llerena, A., Sjöqvist, F., Eliasson, E. and Dahl, M.-L.: Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin. Pharmacol. Ther., 71: 89-98 (2002).
19. Williams, P. A., Cosme, J., Ward, A., Angove, H. C., Matak Vinkovic, D. and Jhoti, H.: Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature, 424: 464-468 (2003).
20. Takahashi, H. and Echizen, H.: Pharmacogenetics of warfarin elimination and its clinical implications. Clin. Pharmacokinet., 40: 587-603 (2001).
21. Gonzalez, F. J. and Gelboin, H. V.: Role of human cytochromes P450 in the metabolic activation of chemical carcinogens and toxins. Drug Metab. Rev., 26: 165-183 (1994).
22. Rendic, S.: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab. Rev., 34: 83-448 (2002).
23. Tsuda-Tsukimoto, M., Ogasawara, Y. and Kume, T.: Pharmacokinetics and metabolism of TR-14035, a novel antagonist of a4β1/a4β7 integrin mediated cell adhesion, in the rat and dog. Xenobiotica, 35: in press.
24. Wester, M. R., Yano, J. K., Schoch, G. A., Yang, C., Griffin, K. J., Stout, C. D. and Johnson, E. F.: The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0-á resolution. J. Biol. Chem., 279: 35630-35637 (2004).