In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilol

Drug Metabolism and Disposition

Volumn 25, Issue 8, 1997, Pages 970-977

  Oldham, Harriet G ^a   Clarke, Stephen E ^b  

^a GLAXOSMITHKLINE   (United Kingdom)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

1 HYDROXYPHENYLCARVEDILOL; 4' HYDROXYPHENYLCARVEDILOL; 5' HYDROXYPHENYLCARVEDILOL; 8 HYDROXYCARBAZOLYLCARVEDILOL; CARVEDILOL; CYTOCHROME P450; CYTOCHROME P450 INHIBITOR; FURAFYLLINE; KETOCONAZOLE; NORCARVEDILOL; QUINIDINE; SULFAPHENAZOLE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; CORRELATION FUNCTION; DEMETHYLATION; DRUG DISPOSITION; DRUG HYDROXYLATION; DRUG METABOLISM; ENANTIOMER; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; HUMAN TISSUE; LIVER MICROSOME; LYMPHOBLASTOID CELL; PHENOTYPE; PRIORITY JOURNAL;

ADRENERGIC BETA-ANTAGONISTS; CARBAZOLES; CELLS, CULTURED; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; ISOENZYMES; MICROSOMES, LIVER; PROPANOLAMINES; STEREOISOMERISM;

EID: 0030848298     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (21)

1. G. Neugebauer, W. Akpan, B. Kaufmann, and K. Reiff: Stereoselective disposition of carvedilol in man after intravenous and oral administration of the racemic compound. Eur. J. Clin. Pharmacol. 38, S108-S111 (1990).
2. G. Neugebauer and P. Neubert: Metabolism of carvedilol in man. Eur. J. Drug. Metab. Pharmacokinet. 16, 257-260 (1991).
3. G. T. McInnes and M. J. Brodie: Drug interactions that matter: a critical reappraisal. Drugs 36, 83-110 (1988).
4. S. A. Wrighton and J. C. Stevens: The human hepatic cytochomes P450 involved in drug metabolism. Critical Rev. Toxicol. 22, 1-21 (1992).
5. S. E. Clarke, A. D. Ayrton, and R. J. Chenery: Characterisation of the inhibition of Cytochrome P4501A2 by furafylline. Xenobiotica 24, 517-526 (1994).
6. S. J. Baldwin, J. C. Bloomer, G. J. Smith, A. D. Ayrton, S. E. Clarke, and R. J. Chenery: Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503A and 2C9. Xenobiotica 25, 261-270 (1995).
7. C. J. Speirs, S, Murray, A. R. Boobis, C. E. Seddon, and D. S. Davies: Quinidine and the identification of drugs whose elimination is impaired in subjects classified as poor metabolizers of debrisoquine. Br. J. Clin. Pharmacol. 22, 739-743 (1986).
8. S. V. Otton, H. K. Crewe, M. S. Lennard, G. T. Tucker, and H. F. Woods: Use of quinidine inhibition to define the role of the sparteine/debrisoquine cytochrome P450 in metoprolol oxidation by human liver microsomes. J. Pharmacol. Exp. Ther. 247, 242-247 (1988).
9. M. Maurice, L. Pichard, M. Daujat, I. Fabre, H. Joyeux, J. Domergue, and P. Maurel: Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture. FASEB J. 6, 752-758 (1992).
10. A. D. Rodrigues: Use of in vitro human metabolism studies in drug development. Biochem. Pharmacol. 48, 2147-2156 (1994).
11. W. H. Schaefer: Formation of a carbamoyl glucuronide conjugate of carvedilol in vitro using dog and rat liver microsomes. Drug Metab. Dispos. 20, 130-133 (1992).
12. D. J. Back, P. Stevenson, and J. F. Tjia: Comparative effects of two antimycotic agents ketoconazole and terbinafine on the metabolism of tolbutamide, ethinyloestradiol, cyclosporine and ethoxycoumarin by human liver microsomes in vitro. Br. J. Clin. Pharmacol. 28, 166-170 (1989).
13. D. J. Back, J. F. Tjia, J. Karbwang, and J. Colbert: In vitro inhibition studies of tolbutamide hydroxylase activity of human liver microsomes by azoles, sulphonamides and quinolines. Br. J. Clin. Pharmacol. 26, 23-29 (1988).
14. J. O. Miners, K. J. Smith, R. A. Robson, M. E. McManus, M. E. Veronese, and D. J. Birkett: Tolbutamide hydroxylation by human liver microsomes, kinetic characterization and relationship to other cytochrome P450 dependent xenobiotic oxidations. Biochem. Pharmacol. 37, 1137-1144 (1988).
15. S. J. Baldwin, J. C. Bloomer, G. J. Smith, A. D. Ayrton, S. E. Clarke, and R. J. Chenery: Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503A and 2C9. Xenobiotica 25, 261-270 (1995).
16. M. E. Veronesse, C. J. Doecke, P. I. Mackenzie, M. E. McManus, J. P. Miners, D. L. P. Rees, R. Gasser, U. A. Meyer, and D. J. Birkett: Site-directed mutation studies of human liver cytochrome P-450 enzymes in the CYP2C subfamily. Biochem. J. 289, 533-538 (1993).
17. D. Sesardic, A. R. Boobis, B. P. Murray, S. Murray, J. Segura, R: De La Torre and D. S. Davies: Furafylline is a potent and selective inhibitor of cytochrome P450 1A2 in man. Br. J. Clin. Pharmacol. 29, 651-663 (1990).
18. C. L. Crespi, E. L. Code, B. W. Penman, and D. J. Waxman: An activity based method for integrating metabolism data from cDNA-expressed cytochrome P450 enzymes to the balance of enzymes in human liver microsomes. ISSX Proceedings 8, 420- (1995).
19. H.-H. Zhou, and A. J. J. Wood: Stereoselective disposition of carvedilol is determined by CYP2D6. Clin. Pharmacol. Ther. 57, 518-524 (1995).
20. M. S. Lennard, G. T. Tucker, J. H. Silas, S. Freestone, L. E. Ramsay, and H. F. Woods: Differential stereoselective metabolism in extensive and poor debrisoquin metabolizers. Clin. Pharmacol. Ther. 34, 732-737 (1983).
21. K. Brosen, J. G. Hansen, K. K. Nielsen, S. H. Sindrup, and L. F. Gram: Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. Eur. J. Clin. Pharmacol. 44, 349-355 (1993).