Pharmacokinetic Parameters of (R)-(−) and (S)-(+)-Flurbiprofen in Dairy Bovines

Abstract

The aim of the study was to evaluate the pharmacokinetics of flurbiprofen (FBP) in different age groups and physiological status groups in dairy cattle. Ten Argentine Holstein bovines were divided into three different groups: 3 cows in early lactation, 3 cows in gestation and 4 newborn calves. Based on previous experience, all the animals received racemic FBP (50:50) at a dose of 0.5 mg/kg by intravenous administration. Blood samples were taken at predetermined times after administration of flurbiprofen. Plasma enantiomer concentrations were measured by HPLC. Total body clearance (ClB) of (S)-(+)-FBP was higher in calves than in cows (114.5, 136.4, 121.4, 128.9 microg/ml vs 22.0, 24.2, 46.5 microg/ml and 27.6, 25.3, 34.6 microg/ml). In calves the disposition kinetics showed stereoselective behaviour. Area under the concentration-time curve (AUC) was higher and Cl(B) and steady-state volume of distribution (V(ss)) were lower for (R)-(-)-FBP than for (S)-(+)-FBP. In cows, stereoselectivity was observed in Cl(B) and elimination half-life (t(1)/2) only in the early lactation group. In this study, enantioselective metabolic behaviour of FBP under the physiological situations studied was found. Hence, it is possible that both enantiomers of flurbiprofen may contribute to the drug's therapeutic effects, but further studies with the administration of separate enantiomers will be required to elucidate their metabolism.