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Effects of Alcohol on the Pharmacokinetics of Morphine Sulfate and Naltrexone Hydrochloride Extended Release Capsules
Author(s) -
Johnson Franklin K.,
Ciric Sabrina,
Boudriau Sophie,
Kisicki James,
Stauffer Joseph
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270011403740
Subject(s) - naltrexone , pharmacokinetics , pharmacology , morphine , bioavailability , crossover study , alcohol , opioid , narcotic antagonist , drug , medicine , anesthesia , chemistry , biochemistry , receptor , alternative medicine , pathology , placebo
Although contraindicated, coingestion of alcohol and opioids by patients or drug abusers is a major health concern because of dangerous additive and potentially life‐threatening sedative and respiratory effects. In addition, alcohol has been shown to disrupt the extended‐release characteristics of certain extended‐release opioid formulations, releasing a hazardous amount of opioid over a short time period. Morphine sulfate and naltrexone hydrochloride extended release capsules (MS‐sNT), which contain naltrexone sequestered in each pellet core, are indicated for management of chronic, moderate to severe pain. Sequestered naltrexone is designed for release upon product tampering (crushing) to potentially mitigate morphine‐induced subjective effects. This open‐label, single‐dose, 4‐way crossover, pharmacokinetic drug interaction study compared the relative bioavailability of morphine and naltrexone when MS‐sNT is administered (under fasting conditions) with increasing doses of alcohol. Thirty‐two healthy, opioid‐naive adults were randomized to MS‐sNT administered with 240 mL of 4%, 20%, or 40% alcohol or water. No drug interaction was found between morphine in MS‐sNT and 4% or 20% alcohol. Administration with 40% alcohol did not affect overall morphine exposure but was associated with a 2‐fold increase in C max and reduction of t max from 9 to 4 hours versus MS‐sNT taken with water. Naltrexone sequestering was successful in all treatment arms and not affected by coadministration with alcohol over the dose range tested.