The metabolism of fenclofenac in the horse

14C-Fenclofenac (2-(2'-4'-dichlorophenoxy)-phenylacetic acid) was administered orally to horses, and urinary metabolites investigated by chromatography. Fenclofenac was rapidly absorbed and eliminated, with a plasma half-life (t1/2) of 2.3 h, with 83.2 and 85.8% of the dose being recovered in the urine in 0-24 h. The major urinary metabolite was the ester glucuronide (58.8, 70.0% dose), and evidence is presented that this metabolite undergoes a structural rearrangement to give beta-glucuronidase-resistant isomers. The other 14C-labelled components in horse urine were unchanged fenclofenac (13.1, 11.5% dose), and two minor metabolites, one of which was identified as a monohydroxy fenclofenac. This study is the first to show an ester glucuronide to be the major metabolite of a non-steroidal anti-inflammatory drug in the horse.