Analgesic, antiinflammatory, and antipyretic effects of S(+)-ketoprofen in vivo.
Many studies indicate that the S-enantiomers of arylpropionic (APA) nonsteroidal antiinflammatory drugs (NSAIDs) are the pharmacologically active enantiomers. S(+)-ketoprofen (dexketoprofen) stereoselectively inhibits cyclooxygenase (COX) in vitro but very little is known about the differential activity of ketoprofen enantiomers in vivo. We examined the analgesic, antiinflammatory, and antipyretic activities of S(+)-ketoprofen in rats and mice. First, we measured the antinociceptive action of S(+)-ketoprofen in abdominal pain models. After intravenous administration. 0.5 mg/kg S(+)-ketoprofen inhibited 92.1+/-2.2% of writhing in mice. Stereoselectivity in the activity was detected; intravenous administration of the R(-)-enantiomer resulted in no statistically significant activity in a dose range of 0.15-1 mg/kg. Similar results were obtained after oral administration in mice. In the rat, S(+)-ketoprofen was a more potent analgesic than diclofenac by both intravenous and oral administration. There was no significant difference between the analgesic effect of S(+)-ketoprofen treatment and the twofold dose of the racemic form in both the mouse and rat models. Second, we measured the antiinflammatory activity of S(+)-ketoprofen using a carrageenan-induced paw edema model in the rat. Intravenous administration of 5 mg/kg of S(+)-ketoprofen almost completely inhibited edema formation. After oral administration, S(+)-ketoprofen is both more potent and effective than diclofenac. Third, we measured antipyretic activity. S(+)-ketoprofen showed a marked antipyretic action (ED50 = 1.6 mg/kg) and was the most potent of the NSAIDs tested. S(+)-ketoprofen is a potent antiinflammatory, analgesic, and antipyretic agent in vivo, consistent with its potent anti-COX activity.
Cabré
F
F
R&D Department, Laboratorios Menarini S.A., Badalona, Spain. fcabre@menarini.es
Fernández
M F
MF
Calvo
L
L
Ferrer
X
X
García
M L
ML
Mauleón
D
D
D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005334:Fever / Q000188:drug therapy; D007275:Injections, Intravenous; D007660:Ketoprofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D013237:Stereoisomerism; D014325:Tromethamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014325:Tromethamine; D002351:Carrageenan; D007660:Ketoprofen; C118296:dexketoprofen trometamol