EFFECT OF THE ENANTIOMERS OF FLURBIPROFEN, IBUPROFEN, AND KETOPROFEN ON INTESTINAL PERMEABILITY

Numerous studies have demonstrated that the administration of nonstero idal anti-inflammatory drugs (NSAIDs) increases small intestinal perme ability, and this has been suggested to be a prerequisite to enteropat hy. If is believed that the inhibitory effect of chiral NSAIDs on the synthesis of prostaglandins and hence their efficacy and toxicity are mainly due to the S enantiomer. Using the urinary excretion of [Cr-51] -EDTA, we have investigated the effects of three nonsteroidal antiinfl ammatory drugs (flurbiprofen, ibuprofen, and ketoprofen) on small inte stinal permeability in rats. Single doses of each NSAID were administe red orally as either the racemate or the R or S enantiomer, the enanti omer dose being half that of the racemate. Each treatment caused a sig nificant increase in intestinal permeability above that seen in untrea ted animals. The R enantiomers of all three NSAIDs increased small int estinal permeability significantly above base line, which was expected for (R)ketoprofen and (R)-ibuprofen due to substantial chiral R to S inversion. The intestinal permeability for (R)-flurbiprofen, although minimal and likely due to 10% inversion, may also suggest prostagland in-independent involvement, Furthermore, (S)-flurbiprofen, used at one -half the dose of the racemate, increased permeability to a similar ma gnitude as the racemate. This observation was similar to that previous ly reported for etodolac. A stereochemically pure enantiomer does not necessarily offer a safer alternative than its racemic form.