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Assessment of Alcohol-Induced Dose Dumping with a Hydrocodone Bitartrate Extended-Release Tablet Formulated with
Mona Darwish1,2, Mary Bond3, Ronghua Yang1
1Teva Pharmaceuticals, 41 Moores Road, PO Box 4011, Frazer, PA, 19355, USA.
Background:
Greater drug content requirements for extended-release (ER) opioids necessitate greater protection against dose dumping. Hydrocodone ER employs the CIMA(®) Abuse-Deterrence Technology platform, which provides resistance against rapid release of the active moiety when the tablet is manipulated or taken with alcohol.
Objective:
Assess effects of alcohol on hydrocodone ER pharmacokinetics.
Study Design:
Open-label, crossover (January 25-April 30, 2010).
Setting:
Single center.
Participants:
Forty healthy adults.
Intervention:
Subjects received all four treatments in a randomized manner (separated by a minimum 5-day washout): hydrocodone ER 15 mg with 240 mL water and 240 mL orange juice containing 4, 20, and 40% alcohol in a fasted state. Naltrexone was administered to minimize opioid-related adverse events.
Main Outcome Measure:
Effect of alcohol on pharmacokinetics of hydrocodone ER assessed by comparing systemic exposure [maximum plasma drug concentration (Cmax) and area under the plasma drug concentration-versus-time curve from time 0 to infinity (AUC0-∞)] after administration with alcohol or with water.
Results:
Geometric means ratios of hydrocodone ER with 4, 20, and 40% alcohol relative to water were 1.05, 1.09, and 1.14, respectively, for Cmax and 1.07, 1.13, and 1.17, respectively, for AUC0-∞. All 90% confidence intervals for these geometric means ratios fell within the limits of 0.8 and 1.25. Increasing alcohol concentrations did not notably affect systemic exposure but were associated with increased adverse events.
Conclusions:
Hydrocodone ER tablets were resistant to dose dumping when administered with alcohol in healthy subjects based on similar systemic exposures observed across all treatments.