Relative Oral Bioavailability of an Abuse-Deterrent, Immediate-Release Formulation of Oxycodone, Oxycodone ARIR in a Randomized Study

Abstract

IntroductionOxycodone ARIR is a novel oral, abuse-deterrent, immediate-release (IR) formulation with physical and chemical properties that deter misuse and abuse by non-oral routes. In this single-dose pharmacokinetic study, we assessed the relative bioavailability of oxycodone for Oxycodone ARIR and IR oxycodone, and the effect of food on Oxycodone ARIR following oral administration.MethodsThis open-label, randomized study in healthy adults compared the relative bioavailability of Oxycodone ARIR 30 mg to IR oxycodone 30 mg under fasted conditions, and Oxycodone ARIR under fed versus fasted conditions. Pharmacokinetic parameters included area under the concentration–time curve from time 0 to the last measured concentration (AUC0–t) and the maximum oxycodone plasma concentration (Cmax). Equivalence was determined using an analysis of variance of the least-squares means.ResultsFifty-eight subjects completed the study. Under fasted conditions, AUC0–t was 4% lower (90% CI 92.5–98.7%) and mean Cmax was 14% lower (90% CI 78.8–94.3%) for Oxycodone ARIR versus IR oxycodone. AUC0–t was 23% higher (90% CI 119.1–127.0%) and mean Cmax was higher (90% CI 108.6–129.4%) when Oxycodone ARIR was administered in the fed versus fasted state. Common adverse events included nausea, headache, and dizziness.ConclusionIn this single-dose pharmacokinetic evaluation, fasted Oxycodone ARIR 30 mg had similar bioavailability to and is expected to have the same efficacy and safety profile as IR oxycodone. When administered in the fed state, pharmacokinetic parameters were slightly higher; however, these differences were considered not clinically meaningful and show that Oxycodone ARIR can be administered with or without food.FundingThis study was funded by Inspirion Delivery Sciences, LLC. Daiichi Sankyo, Inc. funded the journal’s article processing charges and open access fee.Plain Language SummaryPlain language summary available for this article.

Modeling features of addiction with an oral oxycodone self-administration paradigm

“…In this oral oxycodone self-administration paradigm, female mice consumed more oxycodone (mg/day) during the single bottle phase and higher total dose of oxycodone (mg/kg) compared to males (Fig 1), consistent with previous observations that female rodents self-administer higher doses of opioids than males [3,5,81–84]. The effects of sex on opioid intake, dependence, and abuse liability have been well documented [61,81,85–88], and interact with feeding conditions [89,90] and route of administration [3,38] to influence the bioavailability of oxycodone. While pharmacokinetic influences on sex differences were beyond the scope of our study, others have explored sex-dependent factors that may contribute to different oral oxycodone consumption between females and males.…”