Premium
Comparative metabolism of R(‐)‐fenoprofen in rats and sheep
Author(s) -
SORACI A.,
BENOIT E.,
DELATOUR P.
Publication year - 1995
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1995.tb00574.x
Subject(s) - in vivo , hydroxylation , metabolism , chemistry , in vitro , thioester , biochemistry , medicine , stereochemistry , biology , enzyme , microbiology and biotechnology
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 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 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 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(‐)‐FPF‐CoA, such as incorporation into triacylglycerols and conjugation with amino acids, may be quantitatively more important