Synergism between paracetamol and nonsteroidal anti-inflammatory drugs in experimental acute pain.
The antinociception induced by the intraperitoneal coadministration of combinations of paracetamol with the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, ketoprofen, meloxicam, metamizol, naproxen, nimesulide, parecoxib and piroxicam was studied by isobolographic analysis in the acetic acid abdominal constriction test of mice (writhing test). The effective dose that produced 50% antinociception (ED50) was calculated from the log dose-response curves of fixed ratio combinations of paracetamol with each NSAID. By isobolographic analysis, this ED50 was compared to the theoretical additive ED50 calculated from the ED(50) of paracetamol and of each NSAID alone obtained from ED50 dose-response curves. As shown by isobolographic analysis, all the combinations were synergistic, the experimental ED50s being significantly smaller than the theoretically calculated ED50s. The results of this study demonstrate potent interactions between paracetamol and NSAIDs and validate the clinical use of combinations of these drugs in the treatment of pain conditions.
Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Clasificador 70.000, Santiago 7, Chile. hmiranda@med.uchile.cl
Hugo F
HF
Miranda
Margarita M
MM
Puig
Juan Carlos
JC
Prieto
Gianni
G
Pinardi
D000082:Acetaminophen / Q000627:therapeutic use*; D000208:Acute Disease; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016001:Confidence Intervals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen