Comparative Metabolism of (-)(R)-Fenoprofen in Rats and Sheep

SORACI A.L., BENOIT E., DELATOUR P.

JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS

WILEY-BLACKWELL PUBLISHING, INC

Año: 1995 vol. 18 p. 167 - 171

0140-7783

The chiral inversion of 2-arylpropionic acids occurs in many species. It is a unique reaction specilk to this group of drugs. In this study R-(-)-fenoprofen (R-(-)-FPF) was used as a model compound to investigate metabolic chiral inversion in sheep in vivo and in vitro and to compare the data with the results obtained in rats. Metabolic inversion in sheep was 80%. The apparent mean values of Km and V,, of thioester formation were: 392 p and 2.08 nmol/mln/mg in sheep and 500 p~ and 22 nmoYmin/mg in rats. For hydroxylation. the apparent mean values were V,,: 0.02 nmol/min/mg in rats and 0.01 nmol/min/mg in sheep. There was no correlation between in vitro thioesterification and in vivo chird inversion in sheep as compared to rats. In sheep most of the thloester formed underwent inversion (80%) while in rats, where in vitro thioesteriecation was greater, in vivo inversion was less (42%). In consequence, in rats other metabolic pathways for R(-)-FPF- CoA, such as incorporation into triacylglycerols and conjugation with amino acids, may be quantitatively more important.