Dose-dependent pharmacokinetics of aprindine in healthy volunteers

The disposition of aprindine following a single oral dose can best be described by a two-compartment open model. The mean plasma half-life (t 1/2 beta) increased from 8.0 +/- 2.1 h (SD) after a 25 mg dose of 9.4 +/- 2.9 h after 50 mg and to 15.8 +/- 2.6 h after 100 mg, with a decrease in total plasma clearance (Cl/F) and volume of distribution at steady state (V dss/F) and during beta-phase (V d beta/F). The area under plasma concentration-time curve (AUC), maximum plasma concentration (C max) and the amount of unchanged aprindine excreted in the urine increased in a non-linear fashion with the increase in dose. The t 1/2 beta after multiple oral doses showed a 3-fold increase over the single dose value. These results indicate that aprindine shows dose-dependent non-linear kinetics.