Inhibition of hepatic drug metabolism by quinine

Abstract

The effect of quinine on hepatic drug metabolism has been studied both in vitro and in vivo. After acute administration, quinine increased hexobarbital sleeping time, prolonged zoxazolamine paralysis time, and increased plasma half-life of aminopyrine significantly. This antimalarial was found to inhibit all 4 hepatic drug-metabolizing enzymes investigated: aminopyrine N-demethylase, hexobarbital oxidase, aniline hydroxylase and p-nitroanisole O-demethylase; the inhibition on each enzyme was dose-dependent though the potency of inhibition was greater for the type I substrates (aminopyrine and hexobarbital) than for the type II compounds (aniline and p-nitroanisole). Lineweaver-Burk plots showed that quinine inhibited aminopyrine N-demethylase competitively but its inhibition on aniline hydroxylase was non-competitive. There was no evidence of enzyme induction following repeated administration of quinine (50-100 mg kg -1 , i.p., once daily for 5 days). These results demonstrate that quinine is a potent inhibitor of hepatic drug metabolism both in vitro and in vivo.