EFFECT OF FLUVASTATIN, AN INHIBITOR OF 3-HYDROXY-3-METHYL GLUTARYL COA REDUCTASE, ON DRUG-METABOLIZING-ENZYMES IN RATS

Fluvastatin (FV), a new cholesterol-lowering agent, has been studied f or its effects on hepatic microsomal drug-metabolizing enzymes in male rots. FV was orally administered in dosages of 1, 5, and 30 mg/kg/day for 7 consecutive days. 3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) redu ctase activities were markedly decreased at all dose levels. The amoun t of microsomal protein and the contents of cytochromes P450 and b(5) did not change. No induction of aniline hydroxylase, aminopyrine N-dem ethylase, testosterone hydroxylases (15 alpha-, 7 alpha-, 6 beta-, 16 alpha-, and 16 beta-), anti UDP-glucuronosyltransferase were found. On the other hand, 7-ethoxycoumarin o-deethylase activity was slightly i ncreased and lauric acid omega-1-hydroxylase activity tended to be dec reased after treatment with FV.