Peripheral synergism between tramadol and ibuprofen in the formalin test.
Preclinical Research Analgesics with different mechanisms of action can be combined in order to obtain pharmacological synergism, employing lower doses of each agent, thus diminishing side effects. For instance, an atypical dual analgesic such as tramadol (TMD) and a nonsteroidal anti-inflammatory drug such as ibuprofen (IBU) are good candidates to be evaluated when combined and applied peripherally. The present study was conducted to evaluate possible local synergism between TMD and IBU when combined peripherally using the formalin test in rats. The effects of the individual analgesics and their combinations were evaluated simultaneously using a 5% formalin dilution. Dose-effect curves were determined for TMD (50-400 μg/paw) and IBU (1-100 μg/paw). Experimental effective doses were evaluated and isobolographic analyses were constructed to evaluate TMD-IBU combination synergism. Both drugs produced a dose-dependent analgesic effect when applied separately. Isobolographic analysis showed synergism during phase 1 (0-10 min) and phase 2 (15-60 min) when compared with theoretical doses (P < 0.05), with interaction indexes of 0.06 and 0.09, respectively. The present information supports the peripheral analgesic effect of TMD and IBU, especially when combined at appropriate doses.
Doctorado Institucional en Ingeniería y Ciencia de Materiales, Universidad Autónoma San Luis Potosí, San Luis Potosi, Mexico; Pharmaceutical and Biomedical Sciences PhD Program, University of Liege, Liege, Belgium.
Daniel
D
Chavarria-Bolaños
José
J
Perez-Urizar
Christian
C
Grandfils
Amaury
A
Pozos-Guillén
D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D005557:Formaldehyde; D007052:Ibuprofen / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D014147:Tramadol / Q000008:administration & dosage / Q000627:therapeutic use*
D000700:Analgesics; D004338:Drug Combinations; D005557:Formaldehyde; D014147:Tramadol; D007052:Ibuprofen
formalin test; ibuprofen; multimodal analgesia; tramadol