d‐Propoxyphene kinetics after single oral and intravenous doses in man

Abstract

D-Propoxyphene kinetics was studied in 8 healthy male subjects after single oral doses of d-propoxyphene at 65, 130 and 190 mg and after slow i.v. infusion of 65 mg. Total urinary excretion (7 days) indicated complete oral absorption but systemic availability was reduced corresponding to 1st-pass elimination of 30-70%. There was linearity between oral dose and the corresponding area under the plasma concentration/time curve of d-propoxyphene and the metabolite norpropoxyphene. The kinetic measurements showed 2- to 3-fold interindividual variations: oral clearance, 1.3-3.6 l/min; systemic clearance, 0.6-1.2 l/min; apparent volume of distribution, 700-1800 l; d-propoxyphene half-life (t1/2), 8-24 h; and norpropoxyphene t1/2, 18-29 h. There were pronounced intraindividual dose-independent variations in oral clearance in some subjects. The i.v. concentration curves indicated a 3-compartment distribution model. [The severity and sometimes unpredictable course of d-propoxyphene intoxication have stimulated interest in its clinical kinetics.].