In vitro metabolism of a new neuroprotective agent, KR-31543 in the human liver microsomes: Identification of human cytochrome P450

Archives of Pharmacal Research

Volumn 27, Issue 2, 2004, Pages 239-245

  Hye, Young Ji ^a   Lee, Seung Seok ^a   Yoo, Sung Eun ^b   Kim, Hosoon ^c   Dong, Ha Lee ^c   Lim, Hong ^c   Hye, Suk Lee ^a  

^a Wonkwang University   (South Korea)

^b Korea Research Institute of Chemical Technology   (South Korea)

^c Dongbu Hannong Chemical Co   (South Korea)

Author keywords

CYP3A4; Human liver microsomes; In vitro metabolism; KR 31543

Indexed keywords

BENZOPYRAN DERIVATIVE; COMPLEMENTARY DNA; CYTOCHROME P450; ENZYME INHIBITOR; ISOENZYME; KR 31543; KR-31543; NEUROPROTECTIVE AGENT; TETRAZOLE DERIVATIVE;

ARTICLE; BIOSYNTHESIS; BIOTRANSFORMATION; DRUG ANTAGONISM; DRUG INTERACTION; ENZYMOLOGY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; IN VITRO STUDY; KINETICS; LIVER MICROSOME; MASS SPECTROMETRY; METABOLISM; OXIDATION REDUCTION REACTION; ULTRAVIOLET SPECTROPHOTOMETRY;

BENZOPYRANS; BIOTRANSFORMATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYTOCHROME P-450 ENZYME SYSTEM; DNA, COMPLEMENTARY; DRUG INTERACTIONS; ENZYME INHIBITORS; HUMANS; ISOENZYMES; KINETICS; MASS SPECTROMETRY; MICROSOMES, LIVER; NEUROPROTECTIVE AGENTS; OXIDATION-REDUCTION; SPECTROPHOTOMETRY, ULTRAVIOLET; TETRAZOLES;

EID: 4644363440     PISSN: 02536269     EISSN: 02536269     Source Type: Journal    
DOI: 10.1007/BF02980112     Document Type: Article

References (17)

1. Baldwin, S. J., Bloomer, J. C., Smith, G. J., Ayrton, A. D., Clarke, S. E., and Chenery, R. J., Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503A and 2C9. Xenobiotica, 25, 261-270 (1995).
2. Bork, R. W., Muto, T., Beaune, P. H., Srivastava, P. K., Lloyd, R. S., and Guengerich, F. P., Characterization of mRNA species related to human liver cytochrome P-450 nifedipine oxidase and the regulation of catalytic activity. J. Biol. Chem., 264, 910-919 (1989).
3. Hong, K. W., Kim, K. Y., Lee, J. H., Shin, H. K., Kwak, Y. G., Kim, S. O., Lim, H., and Yoo, S. E., Neuroprotective effect of (2S,3S,4R)-N″- cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2 H-benzopyran-4-yl)-N′-benzylguanidine (KR-31378), a benzopyran analog, against focal ischemic brain damage in rats. J. Pharmacol. Exp. Ther., 301, 210-216 (2002).
4. Kim, J., Ji, H. Y., Lee, S. S., Yoo, S. E., Kim. S. O., Lee, D. H., Lim, H., and Lee, H. S., Metabolism of a new neuroprotective agent for ischemia-reperfusion damage, KR-31543 in the rats using liquid chromatography/electrospray mass spectrometry. Arch. Pharm. Res., 25, 664-668 (2002).
5. Lee, M. H., Bae, S. K., Kim, E. J., Kim, Y. G., Kim, S. O., Lee, D. H., Lim, H., Yoo, S. E., and Lee, M. G., Dose-independent pharmacokinetics of a new neuroprotective agent for ischemia-reperfusion damage, KR-31543, after intravenous and oral administration to rats: hepatic and intestinal firstpass effects. J. Pharm. Sci., 92, 190-201 (2003).
6. Lillibridge, J. H., Liang, B. H., Kerr, B. M., Webber, S., Quart, B., Shetty, B., and Lee, C. A., Characterization of the selectivity and mechanism of human cytochrome P450 inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir mesylate. Drug Metab. Disp., 26, 609-616 (1998).
7. Maurice, M., Pichard, L., and Daujat, M., Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture. FASEB J., 6, 752-758 (1992).
8. Merry, C., Barry, M. G., Ryan, M., Tjia, J. F., Hennesy, M., Eagling, V.A., Mulcahy, F., and Back, D. J., Interaction of sildenafil and indinavir when co-administered to HIV-positive patients. AIDS, 13, F101-F107 (1999).
9. Otton, S. V., Crewe, H. K., Lennard, M. S., Tucker, G. T., and Woods, H. F., Use of quinidine inhibition to define the role of the sparteine/debrisoquine cytochrome P450 in metoprolol oxidation by human liver microsomes. J. Pharmacol. Exp. Therap., 247, 242-247 (1988).
10. Sesardic, D., Boobis, A. R., and Murray, B. P., Furafylline is a potent and selective inhibitor of cytochrome P450 1A2 in man. Br. J. Clin. Pharmacol., 29, 651-663 (1990).
11. Shimada, T., Yamazaki, H., Mimura, M., Inui, Y., and Guengerich, F. P., Interindividual variations in human liver cytochrome P450 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. von Moltke, L. L., Greenblatt, D. J., Grassi, J. M., Granda, B. W., Duan, S. X., Fogelman, S. M., Daily, J. P., Harmatz, J. S., and Shader, R. I., Protease inhibitors as inhibitors of human cytochromes P450: High risk associated with ritonavir. J. Clin. Pharmacol., 38, 106-111 (1998).
13. Wang, J. S., Wen, X., Backman, J. T., Taavitsainen, P., Neubonnen, P. J., and Kivisto, K. T., Midazolam α-hydroxylation by human liver microsomes in vitro: inhibition by calcium channel blockers, itraconazole and ketoconazole. Pharmacol. Toxicol., 85, 157-161 (1999).
14. Watkins, P. B., Wrighton, S. A., Mauel, P., Schuets, E. G., Mendezpicon, G., Parker, G. A., and Guzelian, P. S., Identification of an inducible form of cytochrome P-450 in human liver. Proc. Natl. Acad. Sci. USA, 82, 6310-6314 (1985).
15. Wrighton, S. A., Brian, W. R., Sari, M. A., Iwasaki, M., Guengerich, F. P., Raucy, J. L., Molowa, D. T., and Vandenbranden, M., Studies on the expression and metabolic capabilities of human liver cytochrome P-450 IIIA4 (HLp 3). Mol. Pharmacol., 38, 207-213 (1990).
16. Wrighton, S. A. and Ring B. J., Inhibition of human CYP3A catalyzed 1-hydroxy midazolam formation by ketoconazole, nifedipine, erythromycin, cimetidine and nizatidine. Pharm. Res., 11, 921-924 (1994).
17. Yoo, S. E., Yi, K. Y., Lee, S., Suh, J., Kim, N., Lee, B. H., Seo, H. W., Kim, S. O., Lee, D. H., Lim, H. and Shin, H. S., A novel anti-ischemic ATP-sensitive potassium channel opener without vasorelaxation: N-(6-aminobenzopyranyl)-N′-benzyl-N″-cyanoguanidine analogue. J. Med. Chem., 44, 4207-4215 (2001).