The chiral inversion of 2‐arylpropionic acids occurs in many species. It is a 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 invivoandin vitroand to compare the data with the results obtained in rats. Metabolic inversion in sheep was 80. The apparent mean values of Km andVmaxof thioester formation were: 392 μm and 2.08 nmol/min/mg in sheep and 500 μm and 22 nmol/min/mg in rats. For hydroxylation, the apparent mean values were Vmax: 0.02 nmol/min/mg in rats and 0.01 nmol/min/mg in sheep. There was no correlation betweenin vitrothioesterification and invivochiral inversion in sheep as compared to rats. In sheep most of the thioester formed underwent inversion (80) while in rats, where invitrothioesterification was greater,in vivoinversion 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 quantit
展开▼