EFFECTS OF OFLOXACIN ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF PROCAINAMIDE

Procainamide is a class I antiarrhythmic agent that undergoes active t ubular secretion through the organic cation transport system, with app roximately 50% of a dose excreted in the urine as unchanged drug. The remainder is metabolized to an active metabolite, n-acetyl procainamid e (NAPA). Ofloxacin is a fluoroquinolone antibiotic that is excreted i n the urine as unchanged drug via active tubular secretion and glomeru lar filtration. To test the hypothesis that ofloxacin may interfere wi th the renal elimination of procainamide, 9 healthy volunteers were ra ndomly assigned to receive 1 g of oral procainamide as a single dose w ith or without pretreatment with 400 mg of ofloxacin twice a day for 5 doses. Blood and urine samples it ere obtained and pharmacokinetic pa rameters for procainamide were determined for each treatment period. S tandard 12-lead and signal-averaged electrocardiographic recordings we re used for pharmacodynamic analysis. The mean area under the concentr ation-time curve (AUG) and peak plasma concentration (C-max; mu g/mL) for procainamide increased by 27% and 21%, respectively, and the plasm a clearance for procainamide decreased by an average of 22% with coadm inistration of ofloxacin. Ofloxacin did not significantly influence th e pharmacokinetics of NAPA, nor were pharmacodynamics of procainamide significantly affected by coadministration of ofloxacin. These results suggest that procainamide concentrations should be monitored closely when coadministered with ofloxacin.