Dexibuprofen (S+-isomer ibuprofen) reduces gastric damage and improves analgesic and antiinflammatory effects in rodents.
We determined the analgesic and antiinflammatory actions and the related acute mucosal gastric damage from the active S(+)-isomer ibuprofen (dexibuprofen), in comparison with those of the standard racemic formulation of ibuprofen in rodents. The antinociception was evaluated by hot-plate and tail-flick methods after IV and oral (PO) administration in mice and after PO administration in rats. S(+)-Ibuprofen was at least twice more potent than the ibuprofen racemic formulation. The antiinflammatory action of the test compound, assessed with the abdominal constriction test in mice (IV and PO) and with hind paw edema in rats (IV and PO), was found to be significantly more potent than that of ibuprofen after IV treatment in mice and PO administration in rats. Moreover, the test compound caused significantly less mucosal gastric damage than the racemic formulation administered at identical doses (50 mg/kg PO in rats). In conclusion, the S(+)-ibuprofen isomer was found to be more potent than the racemic formulation in analgesic and antiinflammatory tests and presented fewer gastric toxic effects. On the basis of the results of this work, we suggest that the administration of chemical entities, such as R(-)-ibuprofen, should be avoided if they are not essential for the anticipated therapeutic activity.


CONCLUSIONS
Ibuprofen is a nonsteroidal antiinflammatory drug often prescribed as a racemic formulation. We studied the analgesic and antiinflammatory effects of the active S(+)-isomer. The S(+)-ibuprofen was found to be more potent than the racemic formulation and produced less acute gastric damage.
Bonabello
A
A
*Research Department, SPA-Societa' Prodotti Antibiotici S.p.A., Milan, Italy; and Departments of †Anatomy, Pharmacology and Forensic Medicine and ‡Internal Medicine, University of Turin, Turin, Italy.
Galmozzi
M R
MR
Canaparo
R
R
Isaia
G C
GC
Serpe
L
L
Muntoni
E
E
Zara
G P
GP
D000698:Analgesia; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use* / Q000633:toxicity; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D007052:Ibuprofen / Q000627:therapeutic use* / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017288:Pain Threshold; D051381:Rats; D017207:Rats, Sprague-Dawley
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002351:Carrageenan; D007052:Ibuprofen