Objective: This randomized, open-label, crossover study assessed the effect of increasing concentrations of alcohol on the pharmacokinetics of hydrocodone extended release (ER) formulated using novel Teva abuse-deterrence technology.
Methods: Healthy subjects were randomized to receive each of the following regimens once separated by ≥5 days: hydrocodone ER 15 mg (under fasting conditions) with 240 mL of water or orange juice containing 4%, 20%, or 40% alcohol. Naltrexone was administered to block opioid receptors. Blood samples were collected predose and through 72 hours postdose. Pharmacokinetic parameters included peak plasma hydrocodone concentration (Cmax) and area under the plasma hydrocodone concentration-time curve to infinity (AUC0-∞).
Results: Thirty subjects were evaluable for at least 1 pharmacokinetic comparison. Geometric mean Cmax with 0%, 4%, 20%, or 40% alcohol was 11.8-12.4, 13.2, 13.5, and 13.3 ng/mL, respectively, and geometric mean AUC0-∞ was 186.3-192.8, 207.6, 219.7, and 212.9 ng•hr/mL, respectively. The 90% confidence intervals for the ratio of log-transformed Cmax and AUC0-∞ fell within bioequivalence limits (0.8 and 1.25) for 4%, 20%, and 40% alcohol. No appreciable differences in the shapes of mean plasma hydrocodone concentration-time profiles were observed. No serious adverse events (AEs) were reported; incidence of AEs increased with increasing concentrations of alcohol (25%, 57%, and 61% with 4%, 20%, and 40% alcohol, respectively).
Conclusions: This hydrocodone ER formulation was resistant to dose dumping when administered with alcohol. Systemic exposures (Cmax, AUC0-∞) were similar with alcohol and water. Hydrocodone ER was generally well tolerated, with no unexpected AEs in healthy, naltrexone-blocked subjects.