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 investiga te metabolic chiral inversion in sheep in vivo and in vitro and to com pare the data with the results obtained in rats. Metabolic inversion i n 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 a nd 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. Th ere was no correlation between in vitro thioesterification and in vivo chiral inversion in sheep as compared to rats. In sheep most of the t hioester formed underwent inversion (80%) while in rats, where in vitr o 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 acid s, may be quantitatively more important.