Pharmacokinetic properties of combination oxycodone plus racemic ibuprofen: Two randomized, open-label, crossover studies in healthy adult volunteers

Abstract

Background: As part of ongoing studies to evaluate the analgesic efficacy and pharmacokinetic properties of combination oxycodone plus ibuprofen in the treatment of moderate to severe acute pain, 2 pharmacokinetic studies were conducted. Objectives: The goals of these studies were to compare the pharmacokinetic properties of monotherapy with oxycodone or ibuprofen with those of a tablet formulation of these 2 agents combined (study A), and to determine whether the absorption of the individual agents when given in the combination tablet was affected by the concomitant ingestion of food (study B). Methods: Study A was a single-center, open-label, randomized, single-dose, 3-period, 3-way, crossover study Healthy male subjects received oxycodone 5 mg, ibuprofen 400 mg, or a combination tablet containing both, after an overnight fast of ≥8 hours, on study days 1, 8, and 15. Study B was a single-center, open-label, randomized, single-dose, single-crossover study. Healthy volunteers received a tablet containing a combination of oxycodone 5 mg plus ibuprofen 400 mg after either an overnight fast of ≥8 hours or a standardized high-fat breakfast. Both studies included a washout period of ≥7 days between treatments. In both studies, the pharmacokinetic properties (C max, T max, t 1/2, AUC 0-4, AUC 0-1, and AUC 0-∞) of oxycodone and ibuprofen were derived from plasma drug concentrations. Analysis of variance was used to determine and compare pharmacokinetic properties. Results: Twenty-four healthy, white, male subjects were included in study A (mean age, 26.0 years; mean body weight, 71.3 kg; mean height, 170.0 cm). Study B involved 12 subjects (11 men, 1 woman; mean age, 24.8 years; mean body weight, 77.2 kg; mean height, 181.4 cm). The pharmacokinetic properties of ibuprofen and oxycodone were not statistically different when administered alone or combined. Food intake did not affect the rate of oxycodone absorption (90% Cl of C max of fasted state vs fed state, 103–130), or the rate (90% Cl of C max of fasted state vs fed state, 72–95) or extent (90% Cl of AUC 0-∞ of fasted state vs fed state, 88–102) of ibuprofen absorption. The extent of oxycodone absorption was slightly increased when the combination was given with food (90% Cl of AUC 0-∞ of fasted state vs fed state, 115–127). Conclusions: The single-dose pharmacokinetic profiles of oxycodone and ibuprofen in these healthy volunteers were similar when these 2 drugs were given as monotherapy or in combination, suggesting bioequivalence. Food intake before administration of a single dose of the combination did not affect ibuprofen absorption but marginally increased the extent, but not the rate, of oxycodone absorption.