COMPARATIVE ENANTIOSELECTIVITY IN THE EXC RETION OF THE GLUCURONIDES OF CARPROFEN IN MAN, DOGS AND HORSES

After administration of the racemic drug, the stereoselective quantifi cation of the enantiomers of free and conjugated carprofen was perform ed in human plasma and in plasma, urine and bile of dogs and horses. I n humans, the plasma profile of free carprofen and its glucuronides is not stereoselective and the glucuronides excreted in urine are close to a racemate. In dogs and horses on the contrary, the R(-) enantiomer of the free drug is predominant in plasma, while urine and/or bile co ncentrations of the glucuronides are high in comparison to plasma with a strong selectivity for the S(+) enantiomer. Because glucuronidation of carprofen, as a carboxylic compound, is known to be the major meta bolic pathway in most species, interspecies discrepancies in the stere oselective disposition of carprofen seem to be mainly related to the s tereoselectivity in the excretion of the glucuronides. Finally, the hi gh plasma concentrations of carprofen glucuronides in human in compari son to other animal species suggest that the former could be specifica lly subjected to immunological side effects in the time course of trea tments by this type of compounds.