(-)-R-FENOPROFEN - FORMATION OF FENOPROFENYL-COENZYME-A BY RAT-LIVER MICROSOMES

The thioesterification of fenoprofen (FPF) by rat liver microsomes has been studied using an HPLC method enabling direct quantification of the FPF-CoA produced. Over the concentration range studied (5-400 mu M), studies showed the participation of a single CoA ligase in the formation of FPF-CoA, in contrast with the involvement of several isozymes with different affinities, that has been found with ibuprofen (IPF). The K-m for the reaction was dependent upon the presence of non-ionic detergent, a concentration of 0.05% Triton X-100 reducing the K-m from 397 to 20 mu M although the detergent had no effect on V-max. The microsomal long-chain fatty acid CoA ligase was markedly enantioselective towards (-)-R-FPF and the formation of (-)-R-FP-CoA was inhibited by both the (+)-S enantiomer and palmitic acid.