Effects of Camptothecin Analogue CPT-11 on the Activities of Drug Metabolizing Enzymes in Liver Microsomes of Rats.
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We studied whether CPT-11 had an ability to induce activities of drug metabolizing enzyme system in rats.<BR>1. After administration of CPT-11 at a dose of 0.8 (maximal tolerated dose), 4.0 (minimum toxic dose) and 20.0 (lethal dose for 4 weeks succesive administrations) mg/kg for 5 days, the decrease of body weight and liver weight was dose-dependent while the increase of microsomal protein content was not dose-dependent and disappeared 1 week after withdrawal of this compound.<BR>2. Hepatic content of cytochrome P-450 and b, was unchanged by the administration of the test compound at any dose.<BR>3. Slight decrease in aminopyrine N-demethylase and aniline hydroxylase activities was observed in the highest dosage group. These changes were reversible.<BR>4. In vitro, CPT-11 could not inhibit aminopyrine N-demethylase and aniline hydroxylase activities in liver miorosomes obtained from untreated, phenobarbital and 3-methylcholanthrene treated rats.<BR>From these results, we conclude CPT-11 dose not affect the drug metabolizing enzyme system.
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