Non-linear pharmacokinetics of aprindine hydrochloride in oral administration

The pharmacokinetics of oral aprindine hydrochloride (in the following briefly called aprindine; Aspenon) were studied in 38 patients with ventricular premature contractions following single or multiple administration. Oral administration of aprindine in a single dose of 100-150 mg resulted in a mean maximal plasma concentration of 0.77 microgram/ml and a mean elimination half-life of 26.5 h. With multiple oral administration in 10 mg and 20 mg doses at intervals of 8 h, plasma concentration reached a steady state in 1-2 weeks with either dosage rate. Stable plasma concentrations were maintained with little diurnal or day-to-day fluctuation. The mean steady-state minimal plasma concentration with a 10 mg dosage was 0.28 microgram/ml. With a 20 mg dosage, however, this was more than tripled to 0.89 microgram/ml. The elimination process after the final administration of the drug was slower than with single dosage, and deviated from the first-order kinetics to produce a convex curve on a semilogarithmic graph paper. From these results it was apparent that aprindine shows non-linear pharmacokinetic behavior within the therapeutic dosage range.