Pharmacokinetics and bioavailability of carprofen in sheep

The aim of this study was to determine the pharmacokinetics and bioavailability of carprofen in sheep following single intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations of a parenteral formulation at a dose of 4 mg/kg. A total of eight sheep were used for the investigation. The study comprised four periods, according to a crossover design with a 21-day washout period between treatments. Plasma concentrations of carprofen were measured using HPLC-UV. Pharmacokinetic parameters were estimated by non-compartmental model analysis. Following IV administration, t(1/2 lambda z), Cl-T, and V-dss were 43.36 h, 1.98 ml/h/kg, and 121.36 ml/kg, respectively. The C-max(obs) was 26.57 mg/ml for the IM, 23.76 mg/ml for the SC, and 15.90 mg/ml for the PO. The bioavailability following IM, SC, and PO administrations was 75.47%, 82.00%, and 62.51%, respectively. Plasma creatine kinase activity increased significantly at 3, 6, and 12 h following IM administration of carprofen. Despite differences in plasma concentrations and bioavailability among administration routes, carprofen at 4 mg/kg dose may provide the plasma concentration (>1.5 mu g/ml) needed for analgesic effect during 144 h in all routes. However, because of the slow absorption rate after SC and PO routes, the IV route may be preferred primarily for the rapid onset in the analgesic and anti-inflammatory effect of carprofen in sheep. Despite the favorable kinetics, the muscle damage caused by IM injection limits use of carprofen via IM route.