Pharmacokinetics of Ketoprofen After Intravenous and Intramuscular Administrations to Rabbits

The pharmacokinetics of ketoprofen was studied in rabbits following intravenous and intramuscular administrations of ketoprofen, both at a dose of 4.0 mg.Kg-1. Plasma levels of ketoprofen, as a function of time, were determined by a reversed-phase high performance liquid chromatography. The disposition of ketoprofen was described by a two-compartment open model with elimination from the central compartment. A model-independent method using the statistical moment theory was also applied. Pharmacokinetics of ketoprofen was characterized as a drug with terminal half-life of 3.15 hr, low apparent volumes of distribution (V = 0.031 L.Kg-1, Vdss = 0.070 L.Kg-1 and Vdβ = 0.130 L.Kgc-1). The mean residence time (MRT) was found to be 1.44 hr for i.v. injection and 2.86 hr for i.m. injection. The clearance (CL) and apparent volume of distribution at steady state (Vdss) after i.v. injection was determined to be 0.027 L.Kg-1.hr-1 and 0.03 9 L.Kg-1, respectively. The absorption rate constant from the limb muscle site into systemic circulation was calculated 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 ketoprofen after intramuscular administration was determined to be 0.38, relative to the equal i.v dose.