Non-steroidal anti-inflammatory drugs antagonise the constipating effects of tramadol.
We report an antagonistic interaction between tramadol and non-steroidal anti-inflammatory drugs (NSAIDs), on gastrointestinal transit in rats. Transit was evaluated with charcoal and results are expressed as %inhibition. Tramadol and morphine had ED(50)s of 120.70+/-9.54 and 3.20+/-0.26 mg/kg, respectively, while metamizol (85 mg/kg), paracetamol (100 mg/kg) or ibuprofen (50 mg/kg) had no effect. All combinations of tramadol plus an NSAID, resulted in a rightward, non-parallel shift of the curves, which showed (two-way analysis of variance, ANOVA) significant differences from tramadol alone for the dose (P<0.0001), the drug (P<0.0001) and their interaction (P<0.0001), demonstrating antagonism. No interaction was present for morphine plus NSAIDs. The results demonstrate that NSAIDs antagonise the constipating effects of tramadol in rats, a fact that could have clinical relevance when combinations of these drugs are used in pain management in humans.
Planas
Eulalia
E
Department of Pharmacology, Barcelona University School of Odontology, Barcelona, Spain.
Poveda
Raquel
R
Sánchez
Silvia
S
Romero
Asunción
A
Puig
Margarita M
MM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014147:Tramadol / Q000009:adverse effects* / Q000037:antagonists & inhibitors*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014147:Tramadol