title: Dose-response effect of combination hydrocodone with ibuprofen in patients with moderate to severe postoperative pain.
abstract: OBJECTIVE
  The objective of this study was to demonstrate a dose-response effect with 1- and 2-tablet doses of combination hydrocodone 7.5 mg with ibuprofen 200 mg and placebo in patients with moderate to severe postoperative abdominal or gynecologic pain.
  
  
  BACKGROUND
  Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. Previous studies with this combination have demonstrated that the components have an additive analgesic effect as well as efficacy compared with other fixed-dose combination analgesics.
  
  
  METHODS
  This randomized, parallel-group, double-blind, single-dose, placebo-controlled study compared 1 tablet of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), 2 tablets of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), and placebo (n = 60) in patients with moderate or severe pain after abdominal or gynecologic surgery. Analgesia was evaluated over 8 hours.
  
  
  RESULTS
  Mean pain relief (PR) scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.027) and 100 (P = 0.017) minutes and at 2 (P = 0.013), 2.5 (P = 0.012), 3 (P = 0.006), 4 (P = 0.029), 5 (P = 0.002), 6 (P = 0.032), 7 (P = 0.036), and 8 (P = 0.01) hours. Mean pain intensity difference scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.013) and 100 (P = 0.007) minutes and at 2 (P = 0.003), 2.5 (P = 0.002), 3 (P = 0.002), 4 (P = 0.009), 5 (P < 0.001), 6 (P = 0.004), 7 (P = 0.009), and 8 (P = 0.001) hours. Mean total PR scores were significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.01; 0 to 4 hours, P = 0.006; 0 to 6 hours, P = 0.003; 0 to 8 hours, P = 0.003). Mean sum of pain intensity differences was significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.004; 0 to 4 hours, P < 0.001; 0 to 6 hours, P < 0.001; 0 to 8 hours, P < 0.001). Mean peak PR score and median time-to-remedication were significantly greater for the 2-tablet dose than for the 1-tablet dose (P < 0.029 and P = 0.017, respectively). Both doses were superior to placebo. There were no significant differences in the number of patients experiencing adverse events between the 2-tablet dose (n = 6 [10.0%]), the 1-tablet dose (n = 4 [6.7%]), and placebo (n = 1 11.7%]). Adverse events were not serious, and none of the patients discontinued therapy because of side effects.
  
  
  CONCLUSIONS
  This study demonstrated that a 2-tablet dose of hydrocodone with ibuprofen provided significantly more analgesia than a 1-tablet dose (a positive dose-response effect) and that both doses were superior to placebo.
authors.affiliation: Medical Affairs Department, Knoll Pharmaceutical Company, Mount Olive, New Jersey 07828-1234, USA. palangm@basf.com
authors.forename: M
authors.initials: M
authors.lastname: Palangio
authors.forename: G L
authors.initials: GL
authors.lastname: Wideman
authors.forename: M
authors.initials: M
authors.lastname: Keffer
authors.forename: C J
authors.initials: CJ
authors.lastname: Landau
authors.forename: E
authors.initials: E
authors.lastname: Morris
authors.forename: R T
authors.initials: RT
authors.lastname: Doyle
authors.forename: J G
authors.initials: JG
authors.lastname: Jiang
authors.forename: M
authors.initials: M
authors.lastname: Damask
authors.forename: A
authors.initials: A
authors.lastname: de Padova
mesh_terms: D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010149:Postoperative Pain / Q000188:drug therapy*; D010919:Placebos
chemical_list: D004338:Drug Combinations; D010919:Placebos; D006853:Hydrocodone; D007052:Ibuprofen