title: Codeine did not increase analgesic efficacy of coxibs in contrast to that of paracetamol or ibuprofen: isobolographic analysis in mice.
abstract: OBJECTIVE
  There is good evidence that opioids can potentiate analgesic activity of some older non-opioid analgesics (such as paracetamol or ibuprofen) but it is not known whether this also holds true for newer non-opioid analgesics that selectively inhibit cyclooxygenase 2 (coxibs). This study was undertaken to determine the nature of the interaction between codeine and celecoxib or etoricoxib in peritoneal irritation-induced visceral pain in mice. For comparison, interactions of codeine with paracetamol and ibuprofen were also tested using the same method.
  
  
  METHODS
  A small volume of a weak acetic acid (0.6%) was injected into the peritoneal cavity and the number of writhes (contractions of abdominal muscles) was counted. All drugs were given orally. Their interaction was characterized using isobolographic analysis.
  
  
  RESULTS
  Codeine, etoricoxib, celecoxib, ibuprofen and paracetamol all independently produced dose-dependent suppression of writhing. The isobolographic analysis carried out using equipotent dose ratios showed that the interactions between codeine and etoricoxib or celecoxib were sub-additive or additive, respectively. This was in contrast to combinations of codeine with ibuprofen or paracetamol, which were supra-additive. Interaction indexes γ, determined as a ratio between experimental and theoretical ED50 values of the mixture, were as follows: 2.7 for codeine + etoricoxib, 0.62 for codeine + celecoxib, 0.43 for codeine + ibuprofen and 0.33 for codeine + paracetamol.
  
  
  CONCLUSIONS
  These and other results suggest that opioids do not seem to potentiate analgesic effects of selective COX-2 inhibitors, in contrast to nonselective COX inhibitors or paracetamol.
authors.affiliation: Department of Pharmacology, 3rd Faculty of Medicine, Charles University in Prague, Czech Republic. m.janovsky@gmail.com
authors.forename: Martin
authors.initials: M
authors.lastname: Janovsky
authors.forename: Miloslav
authors.initials: M
authors.lastname: Krsiak
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use*; D019342:Acetic Acid / Q000009:adverse effects; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D000068579:Celecoxib; D003061:Codeine / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D000077613:Etoricoxib; D007052:Ibuprofen / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D012044:Regression Analysis; D013449:Sulfonamides / Q000627:therapeutic use; D013450:Sulfones / Q000627:therapeutic use
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D013449:Sulfonamides; D013450:Sulfones; D000082:Acetaminophen; D000068579:Celecoxib; D019342:Acetic Acid; D003061:Codeine; D007052:Ibuprofen; D000077613:Etoricoxib