The relative bioavailability of morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA®) and an extended release morphine sulfate capsule formulation (KADIAN®) in healthy adults under fasting conditions

Franklin K. Johnson, Sabrina Ciric, Sophie Boudriau, James C. Kisicki, Joseph Stauffer

Research output: Contribution to journalArticlepeer-review

Abstract

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 μ-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 (C max) 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%.

Original languageEnglish (US)
Pages (from-to)2-8
Number of pages7
JournalAmerican Journal of Therapeutics
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2011

Keywords

  • bioavailability
  • bioequivalence
  • morphine
  • opioid
  • pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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