Chiral inversion of R(-) fenoprofen and ketoprofen enantiomers in cats

J Vet Pharmacol Ther. 2000 Oct;23(5):265-71. doi: 10.1046/j.1365-2885.2000.00280.x.

Abstract

The chiral inversion process is a characteristic metabolic pathway for different aryl-2-propionic acids or profens. Important variations have been observed between these individual compounds as well as between animal species. In this study, R(-) fenoprofen [R(-)FPF] and R(-) ketoprofen [R(-) KTF] were used to investigate their comparative stereoconversion in cats. After intravenous (i.v.) administration of R(-) FPF, the percentage of chiral inversion was 93.20+/-13.70%. A highly significant correlation (r: 0.978) was observed between the clearance of R(-) FPF and the chiral inversion process. After i.v. administration of R(-) KTF, the percentage of inversion was only 36.73+/-2.8%. No correlation between the clearance of R(-) KTF and this process was observed. R(-) FPF was metabolized by the pathways of thioesterification - chiral inversion processes. For R(-) KTF, the competitive metabolic pathways, glucuronidation and hydroxylation may be involved. However, these metabolic steps are saturable or less functional in cats. Moreover, the thioesterification of R(-) KTF in in vitro studies has been shown to be important in carnivores. The lack of correlation between clearance and chiral inversion process of R(-) KTF may be finally explained by deviation of thioesterification to other metabolic pathways of lipids and/or aminoacid conjugation, particulary glicine derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Area Under Curve
  • Biotransformation
  • Cats / metabolism*
  • Fenoprofen / administration & dosage
  • Fenoprofen / chemistry
  • Fenoprofen / pharmacokinetics*
  • Infusions, Intravenous / veterinary
  • Ketoprofen / administration & dosage
  • Ketoprofen / chemistry
  • Ketoprofen / pharmacokinetics*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Ketoprofen
  • Fenoprofen