Pharmacokinetics of carprofen following single and repeated intravenous administrations of different doses in sheep

Abstract

The aim of this study was to determine the pharmacokinetics of carprofen following single and repeated intravenous (IV) administrations at 1.4 and 4 mg/kg doses in sheep. The study was carried out on twelve sheep in two experiments as single- and multiple-dose pharmacokinetics. In experiment 1, carprofen was administered via IV at single doses of 1.4 (n = 6) and 4 mg/kg (n = 6) in a randomized parallel design. In experiment 2, the same dose groups in experiment 1 following the 21-day washout period received intravenously carprofen every 24 h for 5 days. Plasma concentrations were measured using high-performance liquid chromatography-UV and analyzed by a two-compartment open model. After the single administration of 1.4 mg/kg dose, the t(1/2 alpha), t(1/2el), MRT, Cl-T, V-dss, and AUC were 0.62 h, 27.57 h, 38.78 h, 2.72 ml/h/kg, 105.26 ml/kg, and 515.12 h*mu g/ml, respectively. Carprofen at a single dose of 4 mg/kg showed prolonged t(1/2el) and MRT, and increased V-dss. On day 5 after the repeated administration of the 1.4 mg/kg dose, the t(1/2 alpha), t(1/2el), MRT, Cl-T, V-dss, and AUC were 1.12 h, 57.48 h, 82.18 h, 0.55 ml/h/kg, 45.43 ml/kg, and 2532 h*mu g/ml, respectively. Carprofen at a repeated dose of 4 mg/kg showed increased Cl-T and V-dss and decreased AUC/dose. Although the long t(1/2 lambda z) in single and multiple IV dose studies suggest the possibility of its effective use, the IV route may not be practical in sheep. Therefore, oral and subcutaneous routes of carprofen in sheep would be more valuable in clinical settings.