Presented at the 2012 AAPM Annual Meeting « Back

Single- and Multiple-Dose Pharmacokinetics of Hydrocodone Bitartrate Extended-Release 45 Mg in Healthy Volunteers

Mona Darwish, PhD, mdarwish@cephalon.com1, Mary Bond, MBA MS¹, Philmore Robertson, PhD¹, Cathye Shu, MD PhD¹, William Tracewell, PhD¹, (1) Cephalon, Inc., Frazer, Pennsylvania

Introduction: Hydrocodone is available in the United States only as immediate-release formulations in combination with other medications. This open-label study evaluated the pharmacokinetics and tolerability of single and multiple oral doses of an extended-release formulation of hydrocodone in healthy subjects. Materials and Methods: Subjects received one 45-mg hydrocodone extended-release tablet in Period 1. One 45-mg tablet was administered twice daily from the morning of day 1 through the morning of day 6 in Period 2. Subjects received naltrexone to block opioid receptors. Blood samples for pharmacokinetics were collected pre-dose and through 72 hours post-dose in Period 1 and on day 6 of Period 2. Pharmacokinetic measures included peak plasma concentration (C_max), area under the curve to 72 hours (AUC_0-72), terminal elimination half-life (t_1/2), and steady-state accumulation ratio (R_ss). Safety and tolerability were monitored. The protocol was IRB-approved. Subjects provided written consent. Results: Forty subjects enrolled; 36 completed the study. Mean values after single and multiple doses were C_max, 29.0 and 63.8 ng/mL; AUC_0-72, 561.5 and 1330.1 ng•hr/mL; and t_1/2, 11.1 and 13.2 hours, respectively. R_ss was 1.2. Steady state was achieved within 5 days of twice-daily administration. Four participants discontinued due to adverse events after receiving hydrocodone. No serious adverse events were reported. Conclusions: The pharmacokinetic profile of extended-release hydrocodone was qualitatively similar after single and multiple doses. Extended-release characteristics were observed at steady-state with plasma levels maintained over the 12-hour interval. Exposure (AUC_0-72 and C_max) at steady-state was slightly greater than expected based on single-dose data.

Funding: This study was sponsored by Cephalon, Inc. (Frazer, PA).