EVALUATION OF CARPROFEN IN CALVES USING A TISSUE CAGE MODEL OF INFLAMMATION

The arylpropionate anti-inflammatory drug, carprofen, was administered intravenously as the racemate at a dose rate of 0.7 mg kg(-1) body we ight to six Friesian bull calves aged 16-17 weeks. Anti-inflammatory a nd pharmacokinetic properties were investigated using a tissue cage mo del of inflammation based on intracaveal injection of the mild irritan t, carrageenin. Carprofen displayed enantioselective pharmacokinetics, with the R(-) enantiomer predominating in plasma at all measuring tim es. Elimination half-life and mean residence time were shorter and vol ume of distribution and clearance were greater for the S(+) than for t he R(-) enantiomer. Penetration of both enantiomers into transudate (n on-stimulated tissue cage) was poor but penetration into exudate (carr ageenin-stimulated tissue cage) was good. Carprofen failed to reduce e xudate concentration of prostaglandin E(2) and the reductions in 12-hy droxyeicosatetraenoic acid were non-significant at most sampling times . The long elimination half-life of both R(-) and S(+) carprofen enant iomers and their ready penetration into and slow clearance from inflam matory exudate indicate that the drug is likely to have a long duratio n of action in calves. The mechanism of action is unknown but it is un likely to involve inhibition of either cycle-oxygenase or 12-lipoxygen ase.