Comparative metabolism of R(-)-fenoprofen in rats and sheep.
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 in vivo and in vitro to compare the data with the results obtained in rats. Metabolic inversion in sheep was 80%. The apparent mean values of Km and Vmax of thioester formation were: 392 microM and 2.08 nmol/min/mg in sheep and 500 microM 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 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(-)-FPF-CoA, such as incorporation into triacylglycerols and conjugation with amino acids, may be quantitatively more important.
Soraci
A
A
Department of Metabolic Toxicology, School of Veterinary Medicine of Lyon, Marcy l'Etoile, France.
Benoit
E
E
Delatour
P
P
D000818:Animals; D004951:Esterification; D005279:Fenoprofen / Q000378:metabolism* / Q000493:pharmacokinetics; D006900:Hydroxylation; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D012756:Sheep / Q000378:metabolism*; D013237:Stereoisomerism
D005279:Fenoprofen