PHARMACOKINETICS OF KETOPROFEN AFTER INTRAVENOUS AND INTRAMUSCULAR ADMINISTRATIONS TO RABBITS

The pharmacokinetics of ketoprofen was studied in rabbits following in travenous and intramuscular administrations of ketoprofen, both at a d ose of 4.0 mg.Kg-1. Plasma levels of ketoprofen, as a function of time , were determined by a reversed-phase high performance liquid chromato graphy. The disposition of ketoprofen was described by a two-compartme nt open model with elimination from the central compartment. A model-i ndependent method using the statistical moment theory was also applied . Pharmacokinetics of ketoprofen was characterized as a drug with term inal half-life of 3.15 hr, low apparent volumes of distribution (V(c) 0.031 L.Kg-1, Vd(ss) = 0.070 L.Kg-1 and Vd(beta) = 0.130 L.Kg-1. The m ean residence time (MRT) was found to be 1.44 hr for i.v. injection an d 2.86-hr for i.m. injection. The clearance (CL) and apparent volume o f distribution at steady state (Vd(ss)) injection was determined to be 0.027 L.Kg hr and 0.039 L.Kg-1, respectively. The absorption rate con stant from the limb muscle site into systemic circulation was calculat ed to be 2.19 hr-1 and peak plasma concentration after i.m. injection was observed to be at 0.31 +/- 0.11 hr. The systemic availability of k etoprofen after intramuscular administration was determined to be 0.38 , relative to the equal i.v dose.