title: Median effective dose (ED50) of paracetamol and nefopam for postoperative pain: isobolographic analysis of their antinociceptive interaction.
abstract: BACKGROUND
  The analgesic efficacy of nefopam and of paracetamol has been shown in the postoperative period after mild- and moderate-pain surgery. The aim of this study was to define the median effective analgesic doses of each drug and of their combination, in order to determine the nature of their interaction.
  
  
  METHODS
  Ninety adult patients scheduled to undergo tonsillectomy under general anesthesia were enrolled in one out of three groups: nefopam group, or paracetamol group, or nefopam-paracetamol group. The median effective dose for each drug and also for their combination was defined using an up-and-down sequential allocation technique. The analgesic interaction of their combination was assessed using an isobolographic analysis.
  
  
  RESULTS
  The median effective analgesic dose (median value and 95% confidence interval) of nefopam and paracetamol were 21.7 mg (21.1-22.3 mg) and 628 mg (600-656 mg), respectively. The median effective analgesic doses of the combination were 8.9 mg (8.7-9.1 mg) for nefopam and 265 mg (256-274 mg) for paracetamol. The isobolographic analysis demonstrated a supra-additive interaction of the two drugs.
  
  
  CONCLUSIONS
  The combination of nefopam and paracetamol produces effective analgesia with a synergistic interaction.
authors.affiliation: Department of Anesthesiology, Centre Medico-Chirurgical Saint Paul, Fort de France, Martinique, France. alainvanelstraete@yahoo.fr
authors.forename: A C
authors.initials: AC
authors.lastname: Van Elstraete
authors.forename: P
authors.initials: P
authors.lastname: Sitbon
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000768:Anesthesia, General; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009340:Nefopam / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D010149:Postoperative Pain / Q000188:drug therapy*; D014068:Tonsillectomy
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D009340:Nefopam