Abstract
Although aprindine (AP), an anti-arrhythmic drug, had been shown to follow a non-linear pharmacokinetics in human subjects with a very large inter-subject variability, the metabolic pathways contributing the non-linear pharmacokinetic disposition of AP have not been clarified yet. Pharmacokinetics of AP and its metabolites, p-OHAP, i-OHAP and DEAP, was studied in seven arrhythmic patients administering 20mg to 60mg of AP every 12 hour for 2 weeks, and was evaluated the non-linearity using a mixed effect model analysis. The partial formation clearances of i-OHAP and p-OHAP from AP showed AP dose dependency. Metabolic parameters for formation of metabolites, p-OHAP, i-OHAP and DEAP from AP were obtained using human and rat liver microsomes, and compared. Lower capacities and higher affinities of i-OHAP and p-OHAP formations shown in human microsomes reasonably described of the non-linearity of AP disposition in humans.
