Rac-flurbiprofen is more ulcerogenic than its (S)-enantiomer.
The most common, and sometimes life-threatening, side-effects associated with the human use of the analgesic, nonsteroidal antiinflammatory drugs (NSAIDs) are gastrointestinal. These include gastritis, ulceration, and severe bleeding. The aryl propionic acid class of NSAIDs are among the most widely used of these drugs in the world, including rac-ibuprofen, rac-flurbiprofen, and rac-ketoprofen. Marketed as racemates, it was assumed that the "inactive" (R)-enantiomers, having no cyclooxygenase inhibiting effect, also had no toxic effect. In a 30-day dose response study of (S)-, (R)-, and rac-flurbiprofen given daily over a range of doses the (R)-isomer alone proved to be without apparent gastrointestinal (GI) toxicity. On the other hand the racemate proved to be 2 to 4 times as ulcerogenic in enantiomerically equivalent doses as the (S)-enantiomer. These results have significant clinical implications.
Wechter
W J
WJ
Department of Medicine, School of Medicine, Loma Linda University, CA 92350.
Bigornia
A E
AE
Murray
E D
ED
Levine
B H
BH
Young
J W
JW
D000818:Animals; D004064:Digestive System / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005480:Flurbiprofen / Q000737:chemistry / Q000633:toxicity*; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000473:pathology; D007583:Jejunum / Q000187:drug effects / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014456:Ulcer / Q000139:chemically induced* / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
D005480:Flurbiprofen