ENANTIOSELECTIVE GLUCURONIDATION AND SUBSEQUENT BILIARY-EXCRETION OF CARPROFEN IN HORSES

Carprofen (CPF) enantiomers and their glucuronide conjugates (GLUC) we re measured in plasma and bile of horses after IV administration of th e 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 tr ansiently at low concentration (maximal plasma concentration, 0.5 mu g /ml). The enantiospecific plasma profiles indicated a dear predominanc e of R-CPF, whereas the stereoselectivity of the glucuronides favored S-GLUC. At 1, 2, and 12 hours after administration of the drug, bile c oncentrations of GLUC were high compared with those in plasma and enan tioselectivity favored S-GLUC, These data indicate that the higher bod y clearance observed for S-CPF is a con sequence of the enantioselecti vity in liver glucuronidation and subsequent biliary excretion of the S enantiomer of the drug.