title: Median effective dose (ED50) of nefopam and ketoprofen in postoperative patients: a study of interaction using sequential analysis and isobolographic analysis.
abstract: BACKGROUND
  The analgesic efficacy of ketoprofen has been shown after moderate- and severe-pain surgery, and the analgesic efficacy of nefopam has been shown after moderate-pain surgery. The aim of this study was to define the median effective analgesic doses of each drug and to determine whether the interaction of nefopam and of ketoprofen is synergistic.
  
  
  METHODS
  Seventy-two patients scheduled to undergo moderately painful surgery were enrolled in one of three groups. The dose of nefopam and ketoprofen received by a particular patient was determined by the response of the previous patient of the same group, using an up-and-down technique. Initial doses were 18 and 40 mg, with dose adjustment intervals of 2 and 5 mg, in the nefopam and ketoprofen groups, respectively. The initial doses of nefopam and ketoprofen were 8 and 20 mg, respectively, in the nefopam-ketoprofen group, with the same dose adjustment intervals. Analgesic efficacy was defined as a decrease to less than 3 on a 0-10 numeric pain scale, 45 min after the beginning of drug infusion.
  
  
  RESULTS
  The median effective analgesic dose (median value and 95% confidence interval) of nefopam and ketoprofen were, respectively, 28 mg (17-39 mg) and 30 mg (14-46 mg). The median effective analgesic dose of the combination was 1.75 mg (0.9-2.3 mg) for nefopam and 4.3 mg (2.2-6.5 mg) for ketoprofen.
  
  
  CONCLUSIONS
  The isobolographic analysis demonstrated that the combination of the two drugs produces effective analgesia with an important synergistic interaction.
authors.affiliation: Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, Paris, France.
authors.forename: Noémie
authors.initials: N
authors.lastname: Delage
authors.forename: Hilal
authors.initials: H
authors.lastname: Maaliki
authors.forename: Hélène
authors.initials: H
authors.lastname: Beloeil
authors.forename: Dan
authors.initials: D
authors.lastname: Benhamou
authors.forename: Jean-Xavier
authors.initials: JX
authors.lastname: Mazoit
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007660:Ketoprofen / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009340:Nefopam / Q000008:administration & dosage*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010149:Postoperative Pain / Q000517:prevention & control*; D011446:Prospective Studies
chemical_list: D009340:Nefopam; D007660:Ketoprofen