Dose dependent effect of cimetidine on procainamide disposition in man

This study investigated the influence of single dose of 200 mg and 400 mg cimetidine on the pharmacokinetics of procainamide (PA) in healthy Chinese. The results show that AUC of PA was significantly raised by 38% and 24% with a significant reduction in renal clearance by 40% and 31%, respectively, when single dose of 400 mg or 200 mg cimetidine was coadministered. Significant changes of AUC and renal clearance of the active metabolite--N-acetylprocainamide (NAPA) were found only following the dose of 400 mg cimetidine. The larger dose of cimetidine produced greater alteration in the PA and NAPA pharmacokinetics. The interaction is mainly associated with their reduced renal clearance.