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 intestin al inflammation and promoting repair of injury. In experimental colitis, in hibition of prostaglandin synthesis with nonsteroidal anti-inflammatory dru gs (NSATD) leads to marked exacerbation of tissue injury. It has been sugge sted that the ability of chiral NSAID to inhibit prostaglandin synthesis is completely attributable to the s-enantiomer, while the R-enantiomer is a m uch weaker inhibitor. Thus, it is possible that R-enantiomers of chiral NSA ID will have reduced intestinal toxicity and reduced ability to exacerbate colitis. In the present study, we compared R- and s-enantiomers of two chir al NSAID (flurbiprofen and etodolac) in terms of their ability to exacerbat e colitis in the rat. We found that R-flurbiprofen and R-etodolac did not e xacerbate colitis, in contrast to the S-enantiomers or racemates. The R-ena ntiomers also had significantly less inhibitory activity on prostaglandin s ynthase. Reduced biliary excretion of Retodolac may have also contributed t o the lack of detrimental effects in this model. The results support the hy pothesis that prostaglandins play an essential role in down-regulating colo nic inflammation and promoting repair.