Effects of food and alcohol on the pharmacokinetics of an oral, extended-release formulation of hydrocodone in healthy volunteers

Abstract

Background: The purpose of this study was to evaluate the pharmacokinetics, bioavailability, and safety of oral extended-release hydrocodone (HC-ER) when administered with food or alcohol. Methods: Two single-center, open-label, randomized, crossover studies were conducted in healthy volunteers. In a two-period food-interaction study, 12 subjects received HC ER 20 mg after an overnight fast and a high-fat meal. In a three-period alcohol-interaction study, 30 naltrexone-blocked subjects received HC ER 50 mg with a 0%, 20%, or 40% alcohol/orange juice solution after an overnight fast. Pharmacokinetic parameters were derived from plasma concentrations of hydrocodone and its metabolites. Results: Exposure to hydrocodone after HC ER 20 mg was similar in the fed and fasted states, as assessed by area under the plasma concentration versus time curve from time of dosing to time of last detectable concentration (AUC0–t; 316.14 versus 311.94 ng ⋅ h/mL); relative bioavailability (Frel) was 101.74%. Differences (fed versus fasted) in hydrocodone mean maximum plasma concentration (Cmax; 28.86 versus 22.74 ng/mL) and median time to Cmax (tmax; 6 versus 8 hours) were not clinically significant. Administration of 20% alcohol with HC-ER 50 mg did not increase systemic exposure relative to 0% alcohol (AUC0–t 878 versus 832 ng ⋅ h/mL; Frel 105%) or result in clinically meaningful changes in Cmax (51.8 versus 46.3 ng/mL) or tmax (5.44 versus 6.16 hours). Administration with 40% alcohol increased AUC0–t (1,008 ng ⋅ h/mL versus 832 ng ⋅ h/mL; Frel 120%) and Cmax (109 versus 46.3 ng/mL), and shortened tmax (2.43 versus 6.16 hours). Adverse events occurred in 10.0%, 24.1%, and 66.7% of subjects after 0%, 20%, and 40% alcohol, respectively. Conclusion: HC-ER can be administered without regard to meals. While there was no evidence of “dose-dumping” (an unintended, rapid release in a short time period of all or most of the hydrocodone from HC ER), even with 40% alcohol, as with all opioids, alcohol should not be ingested while using HC-ER.