title: Enantioselective glucuronidation and subsequent biliary excretion of carprofen in horses.
abstract: 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.
authors.affiliation: Department of Basic Sciences and Clinical Biology, School of Veterinary Medicine of Lyon, Marcy-l'Etoile, France.
authors.forename: A
authors.initials: A
authors.lastname: Soraci
authors.forename: E
authors.initials: E
authors.lastname: Benoit
authors.forename: P
authors.initials: P
authors.lastname: Jaussaud
authors.forename: P
authors.initials: P
authors.lastname: Lees
authors.forename: P
authors.initials: P
authors.lastname: Delatour
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D001646:Bile / Q000378:metabolism*; D002227:Carbazoles / Q000097:blood / Q000378:metabolism*; D005965:Glucuronates / Q000097:blood / Q000378:metabolism*; D006736:Horses / Q000097:blood / Q000378:metabolism*; D008297:Male; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D005965:Glucuronates; C007005:carprofen