Lack of effect of cimetidine on the metabolism of quinidine: effect on renal clearance.

The disposition and urinary recovery of unchanged quinidine, (3S)-3-hydroxyquinidine, 2'-oxoquinidinone and quinidine-N-oxide was studied in 5 normal volunteers following a single oral dose of quinidine sulfate (400 mg) with and without cimetidine pre-treatment (1.2 g/day for 7 days). Total amounts of parent compound or metabolites excreted in the urine following cimetidine pre-treatment were not significantly different from that excreted during quinidine alone. Cimetidine reduced the mean apparent oral clearance of quinidine (+/- s.e.m.) by 33% from 23.7 +/- 2.5 to 15.9 +/- 1.7 l/h (p less than 0.05). This 33% decline in oral clearance paralleled the 33% decline in renal clearance of unchanged quinidine which decreased from 56.7 +/- 13.3 to 38.3 +/- 3.3 ml/min. The reduction in quinidine renal clearance associated with cimetidine pre-treatment, although failing to achieve statistical significance, partially accounted for the observed decrease in mean apparent oral clearance. This suggests that cimetidine may compete for renal tubular secretion of unchanged quinidine and its metabolites rather than alter the oxidative metabolism of quinidine.