Variability of inversion of (R)-flurbiprofen in different species

Abstract

The anti-inflammatory activity of 2-arylpropionic acids like flurbiprofen appears to be due to the S enantiomers only. A unique characteristic of the metabolism of this class of drugs is inversion of configuration. The present study examines whether chiral inversion occurs after administration of the optically pure flurbiprofen enantiomers to various species (i.e., dogs, guinea pigs, rats, and gerbils). Concentrations of the enantiomers in plasma were analyzed by a stereoselective high-performance liquid chromatographic assay with a chiral alpha 1-acid glycoprotein column. Pharmacokinetic parameters of the flurbiprofen enantiomers were evaluated with a two-compartment computer model. Inversion of (R)-flurbiprofen to its optical antipode occurred to a variable extent in the dog [fraction inverted (Fi) = 0.39; n = 3] and the guinea pig (Fi = 1.00; n = 3) and to a much lower extent in the rat (Fi = 0.02; n = 3) and the gerbil (Fi = 0.05; n = 3). After intravenous administration of (S)-flurbiprofen to dogs, guinea pigs, rats, and gerbils, (R)-flurbiprofen was not detected in plasma (limit of quantification was 0.05 microgram/100 microL of plasma).