Taxol metabolism in rat hepatocytes.
Biochem Pharmacol
; 46(9): 1661-4, 1993 Nov 02.
Article
em En
| MEDLINE
| ID: mdl-7902091
ABSTRACT
Metabolism of the anticancer drug taxol was investigated in freshly isolated rat hepatocytes. Two main metabolites were separated by reversed-phase HPLC and shown by tandem mass spectrometry to be monohydroxylated metabolites. Kinetic studies revealed apparent Km values of 68 and 61 microM with identical Vmax values for the two metabolites. Verapamil and midazolam, but not phenacetin, showed concentration-dependent inhibition of taxol metabolism with both metabolites being affected equally. The IC50 was about 100 microM for verapamil and 25 microM for midazolam. These observations demonstrate for the first time in vitro metabolism of taxol and suggest that the metabolism may be subject to potentially important interactions with numerous other drugs.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paclitaxel
/
Fígado
Limite:
Animals
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
1993
Tipo de documento:
Article