Effect of Cimetidine on Quinidine Clearance

Cimetidine has been reported to inhibit the hepatic metabolism of numerous drugs. Theoretically cimetidine could inhibit the metabolism of quinidine. This study was undertaken to determine the effect of cimetidine on quinidine plasma concentrations. Nine healthy volunteers were entered into the matched-pairs study. Baseline quinidine pharmacokinetic parameters were determined after a single oral 400-mg dose. Study parameters were determined after 3 days of cimetidine 300 mg p.o. q.i.d., when 400 mg quinidine was again administered. Cimetidine increased the area under the time-concentration curve (14.5%, p less than 0.01), decreased the total body clearance (24.9%, p less than 0.05), and prolonged the half-life (22.6%, p less than 0.05) of quinidine in this study. There was no change in peak quinidine concentrations or time to peak. These data document an interaction between cimetidine and quinidine. The clinical importance of this interaction should be greatest in patients with impaired liver function, patients with preexisting near-toxic plasma concentrations of quinidine, and the elderly. Patients placed on cimetidine and quinidine should be monitored closely for signs and symptoms of quinidine toxicity.