Effects of R- and S-enantiomers of chiral non-steroidal antiinflammatory drugs in experimental colitis

Prostaglandins appear to play an important role in down-regulating intestinal inflammation and promoting repair of injury. In experimental colitis, inhibition of prostaglandin synthesis with nonsteroidal anti-inflammatory drugs (NSATD) leads to marked exacerbation of tissue injury. It has been suggested that the ability of chiral NSAID to inhibit prostaglandin synthesis is completely attributable to the s-enantiomer, while the R-enantiomer is a much weaker inhibitor. Thus, it is possible that R-enantiomers of chiral NSAID will have reduced intestinal toxicity and reduced ability to exacerbate colitis. In the present study, we compared R- and s-enantiomers of two chiral NSAID (flurbiprofen and etodolac) in terms of their ability to exacerbate colitis in the rat. We found that R-flurbiprofen and R-etodolac did not exacerbate colitis, in contrast to the S-enantiomers or racemates. The R-enantiomers also had significantly less inhibitory activity on prostaglandin synthase. Reduced biliary excretion of Retodolac may have also contributed to the lack of detrimental effects in this model. The results support the hypothesis that prostaglandins play an essential role in down-regulating colonic inflammation and promoting repair.