A pharmacokinetic/pharmacodynamic study of controlled-release oxycodone

Abstract

A single-dose, analytically blinded, randomized, crossover study was conducted in 22 healthy male volunteers to compare the bioavailability of one 20 mg with two 10 mg controlled-release (CR) oxycodone tablets. In addition, pharmacodynamic effects were assessed using both objective and subjective measures for up to 48 hr after dosing. The two treatments were bioequivalent, with comparable rates (Cmax of one 20 mg tablet was 109% of two 10 mg tablets; 90% confidence limits: 98.4%-120%) and extents (AUC0-infinity: 107%; 100%-114%) of absorption. In addition, no significant differences between tablets were found for mean values of Tmax, T/12abs, or T/12elim. Correlations between plasma oxycodone concentrations and most pharmacodynamic measures were significant. The strongest correlations were observed for pupil size (r = -0.53) and subjects' assessment of drug effect (r = 0.53), with changes in plasma concentration accounting for more than 25% of the observed changes in these variables. This study demonstrated bioequivalence of two 10 mg and one 20 mg CR oxycodone tablet, with significant correlation between plasma oxycodone concentrations and pharmacodynamic effects in normal volunteers.

Oxycodone-induced conditioned place preference and sensitization of locomotor activity in adolescent and adult mice

“…Oxycodone is a mu-opioid agonist (MOP-r) and has been used for over half century in the United States. Compared with the prototypical MOP-r agonist morphine (also a major metabolite of heroin), potency of oxycodone is approximately twice as high, by the oral route (Benziger et al, 1997). Like morphine, oxycodone has rewarding effects (Rutten et al, 2011).…”

Within-subject comparison of the psychopharmacological profiles of oral oxycodone and oral morphine in non-drug-abusing volunteers

“…One possibility for the differences is that perhaps oral oxycodone has a different psychopharmacological profile than oral morphine. However, only one dose of morphine was tested; furthermore, the 30 mg oxycodone dose (and the 20 mg dose) produced a statistically significantly greater degree of miosis than 40 mg morphine, indicating the dosages were not equipotent on a prototypic physiological response to opioids (e.g., Fedder et al 1984;Martin 1984;Benziger et al 1997). The comparison of 40 mg of morphine to 30 mg of oxycodone was based on a morphine/oxycodone analgesic potency ratio of 1.3:1 reported in a study on cancer-pain patients in severe pain (Kalso and Vainio 1990), but there are other reported analgesic potency ratios (e.g., Foley 1985; Curtis et al 1999).…”

Preoperative administration of controlled-release oxycodone as a transition opioid for total intravenous anaesthesia in pain control after laparoscopic cholecystectomy

“…The pharmacokinetic profile of controlled-release oxycodone contributes to stable plasmatic concentrations for 12 h after oral administration with lower interindividual variations than after controlled-release morphine [13]. Controlled-release oxycodone guarantees constant analgesia after its onset, which occurs in approximately 1 h [14]: its preoperative use may assure adequate postoperative analgesia at patient's awakening in the operating room, regardless of surgery duration.…”