Species differences in the metabolism and excretion of fenclofenac

1. The excretion and metabolism of radiolabelled fenclofenac (2-(2, 4-dichlorophenoxy)phenylacetic acid, Flenac^R) has been studied in five species.

2. In the rat, absorption of oral doses of fenclofenac was virtually complete and elimination occurred mainly by the bile and faeces. The guinea-pig excreted equal amounts of radioactivity in urine and faeces, while in rabbit, baboon and man renal excretion was the more important route.

3. In all species the majority of excreted radioactivity was present as fenclofenac ester glucuronide. Amino acid conjunction with fenclofenac was minimal in all species studied.

4. Mono- and di-hydroxylated metabolites have been detected in urine from guineapig, baboon and man. The major hydroxylated metabolite in baboon urine has been identified as 2-(2,4-dichlorophenoxy)-5′-hydroxyphenylacetic acid.