Guaifenesin enhances the analgesic potency of ibuprofen, nimesulide and celecoxib in mice.
OBJECTIVE
Previously, we found that guaifenesin enhances analgesia induced by paracetamol. The aim of the present study was to determine whether guaifenesin is able to also increase analgesic activity in the non-steroid anti-inflammatory drugs ibuprofen, nimesulide and celecoxib. In addition we investigated the influence of guaifenesin on plasma levels of nimesulide.


METHODS
A model of visceral pain consisting of intraperitoneal injection of acetic acid (writhing test) was used. Levels of nimesulide in plasma were measured by HPLC. All drugs were given orally and tested in mice.


RESULTS
Guaifenesin alone did not produce any antinociceptive effect. Simultaneous administration of guaifenesin (200 mg/kg) and subanalgesic doses of ibuprofen (10 and 30 mg/kg), nimesulide (10 and 20 mg/kg) or celecoxib (1 and 5 mg/kg) resulted in a significant antinociceptive effects. The plasma levels of nimesulide were significantly higher in combination with guaifenesin at 30, 60 and 90 min after oral administration in comparison to nimesulide monotherapy.


CONCLUSIONS
The present results suggest that guaifenesin might enhance the analgesic activity of various non-steroidal anti-inflammatory drugs.
Sliva
Jiri
J
Department of Pharmacology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic. slivaj@seznam.cz
Dolezal
Tomas
T
Sykora
David
D
Vosmanska
Magda
M
Krsiak
Miloslav
M
D019342:Acetic Acid / Q000633:toxicity; D000698:Analgesia; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000068579:Celecoxib; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005100:Expectorants / Q000008:administration & dosage; D006140:Guaifenesin / Q000008:administration & dosage*; D007052:Ibuprofen / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000097:blood / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005100:Expectorants; D011720:Pyrazoles; D013449:Sulfonamides; D006140:Guaifenesin; D000068579:Celecoxib; D019342:Acetic Acid; C012655:nimesulide; D007052:Ibuprofen