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Evaluation of the safety, pharmacodynamic, and pharmacokinetic effects following oral coadministration of immediate‐release morphine with ethanol in healthy male participants
Author(s) -
Setnik Beatrice,
Sokolowska Marta,
Johnson Franklin,
Oldenhof John,
Romach Myroslava
Publication year - 2014
Publication title -
human psychopharmacology: clinical and experimental
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.461
H-Index - 78
eISSN - 1099-1077
pISSN - 0885-6222
DOI - 10.1002/hup.2394
Subject(s) - pharmacodynamics , pharmacokinetics , pharmacology , morphine , ethanol , medicine , chemistry , organic chemistry
Objective This paper aimed to evaluate the effects of coadministered immediate‐release morphine and ethanol on safety, pharmacokinetic, and pharmacodynamic measures. Methods In the first stage of a randomized, double‐blind, placebo‐controlled, crossover study, 16 healthy men with a history of moderate drinking received morphine 50 mg + ethanol 0.7 g/kg, morphine 50 mg + ethanol placebo, and morphine placebo + ethanol 0.7 g/kg. In the second stage, participants received either a lower (30 mg) or higher (80 mg) morphine dose (alone and in combination with ethanol) depending on their tolerability to treatments in stage 1. Safety, pharmacodynamic (including visual analog scales, pupillometry, capnography, and psychomotor and cognitive measures), and pharmacokinetic assessments were conducted. Results With the exception of one severe adverse event (AE), all others were mild or moderate in intensity. Morphine resulted in dose‐related increases in AEs. When morphine was administered with ethanol, similar AEs were observed (dizziness, headache, somnolence, nausea, and vomiting), but these were sometimes more frequent compared with those observed with either drug alone. No consistent additive or interaction effects were observed on pharmacodynamic measures. Ethanol had no apparent effects on the pharmacokinetics of morphine or its metabolites. Conclusions Coadministration of single doses of morphine and ethanol tested in this study did not affect the safety, pharmacodynamics, or pharmacokinetics of morphine or ethanol administered alone. Copyright © 2014 John Wiley & Sons, Ltd.