title: Combination paracetamol and ibuprofen for pain relief after oral surgery: a dose ranging study.
abstract: OBJECTIVE
  Combined paracetamol and ibuprofen has been shown to be more effective than either constituent alone for acute pain in adults, but the dose-response has not been confirmed. The aim of this study was to define the analgesic dose-response relationship of different potential doses of a fixed dose combination containing paracetamol and ibuprofen after third molar surgery.
  
  
  METHODS
  Patients aged 16 to 60 years with moderate or severe pain after the removal of at least two impacted third molars were randomised to receive double-blind study medication as two tablets every 6 h for 24 h of either of the following: two tablet, combination full dose (paracetamol 1000 mg and ibuprofen 300 mg); one tablet, combination half dose (paracetamol 500 mg and ibuprofen 150 mg); half a tablet, combination quarter dose (paracetamol 250 mg and ibuprofen 75 mg); or placebo. The primary outcome measure was the time-adjusted summed pain intensity difference over 24 h (SPID 24) calculated from the 100-mm VAS assessments collected over multiple time points for the study duration.
  
  
  RESULTS
  Data from 159 patients were included in the analysis. Mean (SD) time-adjusted SPID over 24 h were full-dose combination 20.1 (18.0), half dose combination 20.4 (20.8), quarter dose combination 19.3 (20.0) and placebo 6.6 (19.8). There was a significant overall effect of dose (p = 0.002) on the primary outcome. Planned pairwise comparisons showed that all combination dose groups were superior to placebo (full dose vs. placebo p = 0.004, half dose vs. placebo p = 0.002, quarter dose vs. placebo p = 0.002). The overall effect of dose was also significant for maximum VAS pain intensity score (p = 0.048), response rate (p = 0.0094), percentage of participants requiring rescue (p = 0.025) and amount of rescue (p < 0.001). No significant dose effect was found for time to peak reduction in VAS or time to meaningful pain relief. The majority of adverse events recorded were of mild (52.75%) or moderate (40.16%) severity and not related (30.7%) or unlikely related (57.5%) to the study medication.
  
  
  CONCLUSIONS
  All doses of the combination provide safe superior pain relief to placebo in adult patients following third molar removal surgery.
authors.affiliation: AFT Pharmaceuticals Ltd, Takapuna, P O Box 33-203, Auckland, 0740, New Zealand.
authors.forename: Hartley C
authors.initials: HC
authors.lastname: Atkinson
authors.forename: John
authors.initials: J
authors.lastname: Currie
authors.forename: John
authors.initials: J
authors.lastname: Moodie
authors.forename: Simon
authors.initials: S
authors.lastname: Carson
authors.forename: Steven
authors.initials: S
authors.lastname: Evans
authors.forename: James P
authors.initials: JP
authors.lastname: Worthington
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Steenberg
authors.forename: Eileen
authors.initials: E
authors.lastname: Bisley
authors.forename: Chris
authors.initials: C
authors.lastname: Frampton
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*; D014081:Tooth Extraction / Q000009:adverse effects*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D004338:Drug Combinations; D000082:Acetaminophen; D007052:Ibuprofen