Pharmacokinetics of aprindine hydrochloride in a maintenance dose

Aprindine hydrochloride was administered orally to 10 patients with ventricular premature contractions in dosages of 10mg and/or 20mg at intervals of 8 hours. Plasma concentration was analyzed to clarify the process of reaching the steady state and the subsequent elimination state. The plasma concentration reached steady statewithin one to two weeks. There were very little diurnal and day-to-day variations in the plasma concentration, so a stable therapeutic level was maintained. Increased dosages from 30 to 60 mg per day resulted in threefold plasma concentration increase from 0.28 to 0.89μg/ml in steady state. The decline of aprindine hydrochloride after the last dose deviated from first-order kinetics, showing a convex decreasing curve on semilogarithmic graph paper.These results demonstrate nonlinear pharmacokinetics for aprindine hydroch loride.