Abstract

The ability of a series of antimalarial drugs to impair the metabolism of metoprolol in rat and man has been examined. Chloroquine was a potent inhibitor in rat liver microsomes (Ki value for metoprolol alpha-hydroxylation = 0.18 microM and for O-demethylation = 0.36 microM). The other antimalarial drugs also inhibited metoprolol oxidation. Quinine was similar to chloroquine in potency, while quinidine, primaquine and mefloquine were slightly less potent. Chloroquine also inhibited metoprolol oxidation in human liver microsomes, although it was about two orders of magnitude less potent than in the rat and the extent of impairment varied greatly between individual livers. Intraperitoneal administration of chloroquine to anaesthetized rats decreased the clearance of metoprolol (40 mg tartrate salt kg-1 i.p.) to 54, 34, 20 and 26% of the control value at doses of 2.5, 4.0, 25 and 40 mg kg-1, respectively. We conclude that antimalarial treatment might have contributed to a previously reported difference in the metabolic pattern of metoprolol between Caucasians and Nigerians.