Presented at the 2012 AAPM Annual Meeting « Back

Bioavailability of Oxymorphone Extended Release 40 Mg and Crush-Resistant Oxymorphone Extended Release 40 Mg with Ethanol Under Fasted Conditions

William Fiske, PhD, wdfiske@gmail.com¹, Janet Jobes², Qinfang Xiang, PhD², Irma Benedek, PhD¹, (1) Endo Pharmaceuticals Inc., at the time of this study, Chadds Ford, Pennsylvania, (2) Endo Pharmaceuticals Inc., Chadds Ford, Pennsylvania

Introduction: The safety of an extended-release (ER) opioid may be compromised if tampering (e.g., crushing) or coadministration with ethanol causes a precipitous increase in opioid bioavailability (dose dumping). The effects of ethanol on the in vitro dissolution and in vivo pharmacokinetics of oxymorphone ER and oxymorphone crush-resistant formulation (CRF) were evaluated. Previous studies demonstrated bioequivalence of the two formulations and that crushing of oxymorphone CRF does not cause dose dumping. Materials and Methods: In-vitro dissolution rates were measured for oxymorphone ER 40-mg and oxymorphone CRF 40-mg tablets in aqueous solutions of 0%−40% ethanol. In two in-vivo, open-label, randomized, crossover studies with institutional review board approval, fasted healthy volunteers, enrolled with written consent, received single oral doses of oxymorphone ER 40 mg or oxymorphone CRF 40 mg with 240 mL of 0%−40% ethanol. Naltrexone was used to minimize opioid effects. Results: In the in-vitro analyses, dissolution rates of oxymorphone ER and CRF were unaffected in aqueous solutions of ≤40% ethanol. Coadministration of oxymorphone ER or oxymorphone CRF with ethanol 20% and 40% increased oxymorphone peak plasma concentrations (C_max) by 14% to 80% and reduced time to C_max. For both formulations, oxymorphone area under the curve (AUC) and terminal half-life were largely unaffected. Conclusions: Coingestion with ethanol did not cause dose dumping from oxymorphone ER or oxymorphone CRF in terms of overall exposure (i.e., AUC), although C_max increased with ethanol dose.

Funding: This study was supported by Endo Pharmaceuticals Inc., Chadds Ford, PA.