title: Evaluation of the safety, pharmacodynamic, and pharmacokinetic effects following oral coadministration of immediate-release morphine with ethanol in healthy male participants.
abstract: 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.
authors.affiliation: Pfizer Inc., Durham, North Carolina, USA.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Setnik
authors.forename: Marta
authors.initials: M
authors.lastname: Sokolowska
authors.forename: Franklin
authors.initials: F
authors.lastname: Johnson
authors.forename: John
authors.initials: J
authors.lastname: Oldenhof
authors.forename: Myroslava
authors.initials: M
authors.lastname: Romach
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019296:Capnography; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011597:Psychomotor Performance / Q000187:drug effects; D012025:Reflex, Pupillary / Q000187:drug effects; D019966:Substance-Related Disorders / Q000503:physiopathology / Q000523:psychology; D064232:Visual Analog Scale; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D000431:Ethanol; D009020:Morphine
keywords: adverse effects; drug interactions; ethanol; immediate-release morphine; pharmacodynamics; pharmacokinetics