A randomized controlled trial and novel mathematical analysis of the analgesic effect of oxycodone versus paracetamol orodispersible tablets

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 ( k ON ), offset ( k OFF ), 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, t½k ON , 44 (25–67) versus analgesia offset, t½k OFF , 156 (63–552) min, p  < 0.01. For pressure pain, t½k ON equalled t½k OFF : 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.