Enantioselective glucuronidation and subsequent biliary excretion of carprofen in horses

Carprofen (CPF) enantiomers and their glucuronide conjugates (GLUC) were measured in plasma and bile of horses after IV administration of the racemic compound (0.7 mg/kg of body weight). The CPF was detectable in plasma for up to 72 hours after dosing, whereas GLUC appeared early (time for maximal plasma concentration, 1 hour) and was measurable transiently at low concentration (maximal plasma concentration, 0.5 microgram/ml). The enantiospecific plasma profiles indicated a clear predominance of R-CPF, whereas the stereoselectivity of the glucuronides favored S-GLUC. At 1, 2, and 12 hours after administration of the drug, bile concentrations of GLUC were high compared with those in plasma and enantioselectivity favored S-GLUC. These data indicate that the higher body clearance observed for S-CPF is a consequence of the enantioselectivity in liver glucuronidation and subsequent biliary excretion of the S enantiomer of the drug.