RAC-FLURBIPROFEN IS MORE ULCEROGENIC THAN ITS (S)-ENANTIOMER

The most common, and sometimes life-threatening, side-effects associat ed with the human use of the analgesic, nonsteroidal antiinflammatory drugs (NSAIDs) are gastrointestinal. These include gastritis, ulcerati on, and severe bleeding. The aryl propionic acid class of NSAIDs are a mong the most widely used of these drugs in the world, including rac-i buprofen, rac-flurbiprofen, and rac-ketoprofen. Marketed as racemates, it was assumed that the ''inactive'' (R)-enantiomers, having no cyclo oxygenase inhibiting effect, also had no toxic effect. In a 30-day dos e response study of (S)-, (R)-, and rac-flurbiprofen given daily over a range of doses the (R)-isomer alone proved to be without apparent ga strointestinal (GI) toxicity. On the other hand the racemate proved to be 2 to 4 times as ulcerogenic in enantiomerically equivalent doses a s the (S)-enantiomer. These results have significant clinical implicat ions. (C) 1993 Wiley-Liss, Inc.