The Relative Bioavailability of Morphine Sulfate and Naltrexone Hydrochloride Extended Release Capsules (EMBEDA(R)) and an Extended Release Morphine Sulfate Capsule Formulation (KADIAN(R)) in Healthy Adults Under Fasting Conditions.

Author(s): Johnson FK, Ciric S, Boudriau S, Kisicki JC, Stauffer J

Affiliation(s): 1Alpharma Pharmaceuticals, LLC, a wholly-owned subsidiary of King Pharmaceuticals(R), Inc, Bridgewater, NJ; 2Celerion (formerly MDS Pharma Services), Montreal, Quebec, Canada; 3Clinical Pharmacology Sciences Department, Celerion (formerly MDS Pharma Services), Lincoln, NE; and 4Johns Hopkins University School of Medicine, Baltimore, MD.

Publication date & source: 2010-11-10, Am J Ther., [Epub ahead of print]

Morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA, King Pharmaceuticals, Inc., Bristol, TN), indicated for the management of chronic, moderate to severe pain, contain extended release morphine pellets with a sequestered naltrexone core (MS-sNT). If the product is tampered with by crushing, naltrexone, a mu-opioid antagonist, is intended for release to mitigate morphine-induced subjective effects. The primary end point of this randomized 2-way crossover study in healthy fasted volunteers was evaluation of morphine bioequivalence between MS-sNT (treatment A) and morphine sulfate extended release capsules (KADIAN, treatment B). Morphine pharmacokinetics were assessed predose to 72 hours postdose of single 100-mg doses of treatment A or B. Analysis of variance of ln-transformed ratios of least squares mean of the area under the concentration time curve (AUC) from time 0 to last measurable concentration (AUC0-t) and AUC from time 0 to infinity (AUCinf) and maximum serum concentration (Cmax) for treatments A versus B were performed. Ratios and 90% confidence intervals for least squares mean for AUC0-t (102.2%; 98.6-105.9%), AUCinf (97.4%; 91.2-104.1%), and Cmax (93.8%; 82.4-106.7%) indicated bioequivalence between the 2 formulations. When subjects who vomited during the 12-hour dosing interval were excluded, the confidence interval for AUC0-t and AUCinf fell within the 80%-125% range, but the lower limit for Cmax was 76.9%.