Pharmacokinetics of probenecid in sheep

Abstract

Guerrini, V.H., Filippich, L.J., English, P.B., Schneider, J., Cao, G.R. & Bourne, D.W.A. Pharmacokinetics of probenecid in sheep. J. vet. Pharmacol. Therap. 8, 128–135. Six Merino ewes were given 1g (27g/kg) probenecid by the intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes. After i.v. injection, the biological half‐life was 1.55 h and apparent volume of distribution at the steady state (Vd) 0.18l/kg. Body clearance (Cl)and renal clearance (Cl) were 0.12l/h/kg and 0.03l/h/kg, respectively. Approximately 28% of unchanged probenecid was excreted in urine. Plasma probenecid concentrations after i.v., i.m. and s.c. injections were 133, 37, and 31 μg/ml, respectively, at 15 min; 76, 36, and 34μg/ml at 1 h; and 43, 23 and 34μg/ml at 2 h. The average bioavailability of probenecid given by i.m. and s.c. injection was 46% and 34%, respectively. However, after 2 h, probenecid plasma concentrations remained higher when it was given subcutaneously than when it was given intramuscularly. Urine output was correlated positively (P < 0.05) with k and Cl. Urine pH increased significantly (P < 0.01) for the first 2 h, and then steadily declined over the subsequent 6 h. The results suggested that probenecid in sheep was rapidly eliminated because it was rapidly excreted in the normal but alkaline urine. Subcutaneous administration of probenecid in animals may be a useful alternative to oral or i.v. administration. Dr V. H. Guerrini, Department of Pharmacy, University of Queensland, St Lucia, Queensland 4067, Australia. Copyrigh