[Enantioselectivity in the excretion of glucuronides of carprofen in man, dogs and horses].
After administration of the racemic drug, the stereoselective quantification of the enantiomers of free and conjugated carprofen was performed in human plasma and in plasma, urine and bile of dogs and horses. In 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 concentrations 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 metabolic pathway in most species, interspecies discrepancies in the stereoselective disposition of carprofen seem to be mainly related to the stereoselectivity in the excretion of the glucuronides. Finally, the high plasma concentrations of carprofen glucuronides in human in comparison to other animal species suggest that the former could be specifically subjected to immunological side effects in the time course of treatments by this type of compounds.
Delatour
P
P
Département de Toxicologie Métabolique, Ecole Nationale Vétérinaire de Lyon.
Garnier
F
F
Maire
R
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000652:urine*; D002227:Carbazoles / Q000737:chemistry / Q000652:urine*; D004285:Dogs / Q000652:urine*; D005965:Glucuronates / Q000652:urine*; D006736:Horses / Q000652:urine*; D006801:Humans; D008297:Male; D013045:Species Specificity; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D005965:Glucuronates; C007005:carprofen
Enantiosélectivité de l'excrétion des glucuronides du carprofène chez l'homme, le chien et le cheval.