Extensive Metabolizers of Debrisoquine Become Poor Metabolizers during Quinidine Treatment

Abstract

Seven male patients (age 55-75 years) were debrisoquine-tested immediately before and after one week of treatment with quinidine sulphate (200 mg .times. 3-4 day-1). Before quinidine all patients were classified as extensive metabolizers (metabolic ratio 0.1-3.6). During quinidine the formation of 4-OH-debrisoquine was practically abolished and the phenotype of the patients was altered to PM (metabolic ratio 15-51). This is probably due to an inhibition of debrisoquine hydroxylation by quinidine. Inhibition of 4-OH-debrisoquine formation was associated with a disproportionate increase in debrisoquine excretion.