Effects of food and alcohol on the pharmacokinetics of an oral, extended-release formulation of hydrocodone in healthy volunteers

Abstract

BackgroundThe purpose of this study was to evaluate the pharmacokinetics, bioavailability, and safety of oral extended-release hydrocodone (HC-ER) when administered with food or alcohol.MethodsTwo single-center, open-label, randomized, crossover studies were conducted in healthy volunteers. In a two-period food-interaction study, 12 subjects received HC-ER 20 mg after an overnight fast and a high-fat meal. In a three-period alcohol-interaction study, 30 naltrexone-blocked subjects received HC-ER 50 mg with a 0%, 20%, or 40% alcohol/orange juice solution after an overnight fast. Pharmacokinetic parameters were derived from plasma concentrations of hydrocodone and its metabolites.ResultsExposure to hydrocodone after HC-ER 20 mg was similar in the fed and fasted states, as assessed by area under the plasma concentration versus time curve from time of dosing to time of last detectable concentration (AUC0–t; 316.14 versus 311.94 ng · h/mL); relative bioavailability (Frel) was 101.74%. Differences (fed versus fasted) in hydrocodone mean maximum plasma concentration (Cmax; 28.86 versus 22.74 ng/mL) and median time to Cmax (tmax; 6 versus 8 hours) were not clinically significant. Administration of 20% alcohol with HC-ER 50 mg did not increase systemic exposure relative to 0% alcohol (AUC0–t 878 versus 832 ng · h/mL; Frel 105%) or result in clinically meaningful changes in Cmax (51.8 versus 46.3 ng/mL) or tmax (5.44 versus 6.16 hours). Administration with 40% alcohol increased AUC0–t (1,008 ng · h/mL versus 832 ng · h/mL; Frel 120%) and Cmax (109 versus 46.3 ng/mL), and shortened tmax (2.43 versus 6.16 hours). Adverse events occurred in 10.0%, 24.1%, and 66.7% of subjects after 0%, 20%, and 40% alcohol, respectively.ConclusionHC-ER can be administered without regard to meals. While there was no evidence of “dose-dumping” (an unintended, rapid release in a short time period of all or most of the hydrocodone from HC-ER), even with 40% alcohol, as with all opioids, alcohol should not be ingested while using HC-ER.

Single-dose pharmacokinetics of 2 or 3 tablets of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155) under fed and fasted conditions: two randomized open-label trials

“…No effect of food on C max was noted after the 2-tablet dose. These results are consistent with food effects reported for other ER hydrocodone products, where food, particularly a fatty meal, may produce modest increases in hydrocodone C max but have no significant effect on total absorption or require administration on an empty stomach [ 11 , 12 ]. After either IR/ER HB/APAP dose, hydrocodone was rapidly absorbed under all conditions, with no clinically relevant lag in the appearance of plasma concentrations when administered with food.…”

A review of in vivo and in vitro aspects of alcohol-induced dose dumping

“…The effect of alcohol on an oral, extended-release formulation of hydrocodone was evaluated in a threetreatment, three-period crossover study in healthy volunteers (Farr et al 2015). In the first period, 50 mg hydrocodone was administered with 240 mL of either 40% alcohol/orange juice, 20% alcohol/orange juice, or orange juice alone, after an overnight fast.…”

“…Such type of design may reduce study drop-out rates and thereby, associated costs and timelines. (b)To reduce adverse events before dosing the opioid drug, the authors agree with the sponsors' approach of administering naltrexone, an opioid receptor antagonist (Johnson et al 2008;Farr et al 2015).…”

An Analysis of Rescue Medication Utilization from a 3-Month, Randomized, Double-Blind, Placebo-Controlled Study in Patients with Chronic Low Back Pain Treated with Single-Entity, Twice-Daily, Extended-Release Hydrocodone

“…HC‐ER is formulated to provide sustained drug delivery over a 12‐hour period , using a proprietary multiparticulate encapsulation system (Spheroidal Oral Drug Absorption System SODAS®, Alkermes, Dublin, Ireland) . In healthy volunteers, the pharmacokinetics of HC‐ER following a single dose after an overnight fast showed the maximum plasma concentration occurring 4–8 hours after dosing with a clearance half‐time of about 6.5 hours . The SODAS technology, which can be customized to provide the desired release kinetics, has been used in approved sustained release products (e.g., Verelan® [verapamil hydrochloride manufactured by Alkermes Gainesville LLC, Gainesville, GA and distributed by Kremers Urban Pharmaceuticals, Inc., Princeton, NJ], Avinza® [morphine sulfate ER; King Pharmaceuticals Research and Development, Inc., Bristol, TN], and Luvox CR® [fluvoxamine maleate, Jazz Pharmaceuticals, Inc., Palo Alto, CA]).…”