• Cynthia Y Robinson, Christopher M Rubino, and Stephen J Farr.
• Senior Scientific Advisor, Clinical Development, Zogenix, Inc., San Diego, California.
• J Opioid Manag. 2015 Sep 1; 11 (5): 405-15.

ObjectivesTo assess the single-dose and steady-state pharmacokinetics of a single-entity hydrocodone extended-release (ER) formulation in patients enrolled in two separate phase 2 clinical studies.SettingBoth studies were multicenter clinical studies.Subjects And InterventionsIn study 1, 115 subjects with postsurgical pain (bunionectomy) received single doses of 10, 20, 30, or 40 mg hydrocodone-ER, 10 mg hydrocodone/325 mg acetaminophen immediate-release (IR), or placebo. In study 2, 37 subjects with osteoarthritic pain received doses of 10, 20, 30, or 40 mg of hydrocodone- ER twice-daily for 7 days. Venous blood samples were taken periodically up to 24 hours postdosing after the single dose (study 1) or after 7 days of dosing (study 2) and were assayed for concentrations of hydrocodone and its major metabolites.Main Outcome MeasuresStandard pharmacokinetic parameters were estimated by noncompartmental analysis methods.ResultsFollowing a single dose of hydrocodone-ER, Tmax was prolonged to approximately 6 hours at all dose levels of hydrocodone-ER compared with 2.9 hours for the IR formulation. All doses of hydrocodone-ER formulations provided prolonged and sustained release of hydrocodone throughout the 12-hour dosing interval with reduced peak-to-trough fluctuation at steady state compared with hydrocodone/acetaminophen-IR comparator. Both single-dose and steadystate mean Cmax and AUClast values showed reasonable dose-proportionality. Norhydrocodone and hydromorphone plasma concentrations were 32-38 percent and <2.1 percent, respectively, of hydrocodone concentrations in both studies.ConclusionsThe sustained plasma concentrations of hydrocodone support twice-daily dosing with a 12-hour dosing interval.

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