COMPARATIVE METABOLISM OF R(-)-FENOPROFEN IN RATS AND SHEEP

The chiral inversion of 2-arylpropionic acids occurs in many species. It isa unique reaction specific 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-max of thioester formation were: 392 mu M and 2.08 nmol/min/mg in sheep and 500 mu M and 22 nmol/min/mg in rats. For hydroxylation, the apparent mean values were V-max: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 chiral inversion in sheep as compared to rats. In sheep most of the thioester formed underwent inversion (80%) while in rats, where in vitro thioesterification was greater, in vivo inversion was less (42%). In consequence, in rats other metabolic pathways for R(-)-PPF-CoA, such as incorporation into triacylglycerols and conjugation with amino acids, may be quantitatively more important.