title: A randomized controlled trial and novel mathematical analysis of the analgesic effect of oxycodone versus paracetamol orodispersible tablets.
abstract: BACKGROUND
  For effective treatment of acute pain, a rapid onset of action is important. Here we quantify the antinociceptive profile of an orodispersible oxycodone tablet (OOT) in a randomized, double-blind, active comparator (paracetamol orodispersible tablet, POT), crossover study design in a population of healthy volunteers.
  
  
  METHODS
  Twelve female volunteers were randomized to receive 20 mg OOT and 500 mg POT sublingually on two occasions. The electrical pain threshold (EPTh), electrical pain tolerance (EPTol) and pressure pain threshold (PPT) were obtained at regular intervals for 5 h. Time-response data were analysed with a longitudinal pharmacodynamic model characterized by rate constants for analgesia onset (kON ), offset (kOFF ), potency parameter (EFF) and validated with a bootstrap analysis. Values are the median (95% CI) as derived from the bootstrap analysis.
  
  
  RESULTS
  OOT produced a rapid increase in response values. For electrical pain analgesia onset, t½kON , 44 (25-67) versus analgesia offset, t½kOFF , 156 (63-552) min, p < 0.01. For pressure pain, t½kON equalled t½kOFF : 30 (16-48) min. OOT was most potent on EPTol: EFF 0.95 (0.39-1.71), p < 0.01, with similar potencies on EPTh, 0.43 (0.19-0.87) and PPT, 0.40 (0.21-0.67). Paracetamol displayed 14% of the analgesic efficacy of oxycodone.
  
  
  CONCLUSIONS
  The analgesic effect of orodispersible oxycodone was successfully quantified using a mathematical model of analgesia evolution. This method allows quantification of a variety of responses times from sparse data sets. Response times as defined by a 30% increase in response thresholds varied significantly among end points: EPTol 15 min, PPTh 18 min and EPTh 41 min.
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, The Netherlands.
authors.forename: C H
authors.initials: CH
authors.lastname: Martini
authors.forename: P
authors.initials: P
authors.lastname: Proto
authors.forename: E
authors.initials: E
authors.lastname: Olofsen
authors.forename: M
authors.initials: M
authors.lastname: van Velzen
authors.forename: L
authors.initials: L
authors.lastname: Aarts
authors.forename: A
authors.initials: A
authors.lastname: Dahan
authors.forename: M
authors.initials: M
authors.lastname: Niesters
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008962:Models, Theoretical; D010098:Oxycodone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000082:Acetaminophen; D010098:Oxycodone