Effect of food on the pharmacokinetics of the hydrocodone extended-release tablet in healthy volunteers

Abstract

Hydrocodone is available for the treatment of pain in the United States only as immediate-release formulations in combination with other medications. A new extended-release hydrocodone tablet has been developed that employs OraGuard technology, a novel platform that is intended to resist dose dumping when taken with alcohol or when pulverized. Two randomized, open-label, crossover studies were conducted to assess the effect of food on the pharmacokinetics of the hydrocodone bitartrate extended-release tablet (Study 1, 15 mg; Study 2, 90 mg). Each participant received hydrocodone extended-release (15 or 90 mg) in both fed and fasted states with 240 mL of water. Hydrocodone doses were separated by a minimum of 5 (Study 1) or 14 days (Study 2). Subjects had received naltrexone to block opioid receptors. Blood samples were collected pre-dose and through 72 hours post-dose. Pharmacokinetic parameters included peak plasma hydrocodone concentration (Cmax) and area under the plasma hydrocodone concentration-versus-time curve from time 0 to infinity (AUC0-∞). Safety was also assessed. Thirty-one subjects completed Study 1; 35 completed Study 2. In Study 1, geometric mean Cmax in the fed and fasted state was 18.5 and 12.5 ng/mL and geometric mean AUC0-∞ was 210.8 and 193.5 ng•hr/mL, respectively. In Study 2, the corresponding Cmax was 86.1 and 60.6 ng/mL and AUC0-∞ was 1262 and 1135 ng•hr/mL, respectively. In both studies, confidence intervals for AUC met bioequivalence criteria (0.8, 1.25) for the fed and fasted states (Study 1: AUC0-∞ 1.035, 1.111; Study 2: AUC0-∞ 1.055, 1.161), while those for Cmax did not (Study 1: 1.354, 1.548; Study 2: 1.306, 1.509). Cmax was 40-45% higher under fed conditions in both studies. Adverse events were similar in fed and fasted states in Study 1 (36% vs 34%), but higher in the fasted state in Study 2 (16% vs 8%). Sponsored by Cephalon, Inc.