Pharmacokinetics of Khellin in Rabbits: Oral,Intravenous, and Intramuscular Administrations

Abstract

This study was undertaken to investigate the pharmacokinetics of khellin in rabbits following oral, intravenous, and intramuscular administrations. Analysis of khellin in the plasma samples was performed according to a previously developed HPLC method. The data obtained from the rapid intravenous administration experiments fitted the two-compartment open model with β, α, total body clearance (TBC), and volume of central compartment (V_c) of 0.0306 hr^?1, 1.93 hr^?1, 573 ml. hr^?1.kg^?1, and 2.1 liter. kg^?1, respectively. The concentration-time profiles acquired following the administration of sugar-coated tablets of khellin were typical of sustained release formulations with time to peak concentration (t_max) and dose-normalized peak plasma concentration (C_max) of 21 hr and 23 ng. ml^?1.mg^?1.kg, respectively. With the exception of one animal, rapid absorption was obtained following the intramuscular or oral suspension administration with (t_max) ranging from 0.083 to 4 hr. A complete absorption was obtained with intramuscular injection, whereas, the fraction of dose absorbed following oral suspension administration was 38%.