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 for its effects on hepatic microsomal drug-metabolizing enzymes in male rats. 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) reductase activities were markedly decreased at all dose levels. The amount of microsomal protein and the contents of cytochromes P450 and b5 did not change. No induction of aniline hydroxylase, aminopyrine N-demethylase, testosterone hydroxylases (15α-, 7α-, 6β-, 16α-, and 16β-), and UDP-glucuronosyltransferase were found. On the other hand, 7-ethoxycoumarino-deethylase activity was slightly increased and lauric acid ω-1-hydroxylase activity tended to be decreased after treatment with FV.