title: Psychomotor effects, pharmacokinetics and safety of the orexin receptor antagonist suvorexant administered in combination with alcohol in healthy subjects.
abstract: A double-blind crossover study investigated psychomotor effects, pharmacokinetics, and safety of the orexin receptor antagonist suvorexant with and without alcohol. Healthy adults (n=31) were randomized to receive placebo or suvorexant (40 mg) plus placebo solution or alcohol (0.7 g/kg) in each of four treatments (single doses; morning administration). The US Food and Drug Administration approved suvorexant dose is 10 mg (up to 20 mg) daily. Pharmacodynamic effects were assessed using tests of digit vigilance (DVT; primary endpoint), choice reaction time, digit symbol substitution, numeric working memory, immediate/delayed word recall, body sway and subjective alertness. Suvorexant alone did not significantly affect DVT reaction time, but did impact some pharmacodynamic tests. Suvorexant with alcohol increased reaction time versus either alone (mean difference at 2 h: 44 ms versus suvorexant, p<0.001; 24 ms, versus alcohol, p<0.05) and had additive negative effects on tests of vigilance, working/episodic memory, postural stability and alertness. No effects of suvorexant alone or with alcohol were observed by 9 h. No important changes in pharmacokinetic parameters were observed upon co-administration. All treatments were generally well tolerated without serious adverse events. In conclusion, co-administration of 40 mg suvorexant and 0.7 g/kg alcohol had additive negative psychomotor effects. Patients are advised not to consume alcohol with suvorexant.
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Ka Lai
authors.initials: KL
authors.lastname: Yee
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Gill
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Panebianco
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Mangin
authors.affiliation: QPS-Biokinetic, Springfield, MI, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Morrison
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA jackie_mccrea@merck.com.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: McCrea
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Troyer
mesh_terms: D000328:Adult; D001381:Azepines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D004311:Double-Blind Method; D004357:Drug Synergism; D000431:Ethanol / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D000068796:Orexin Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D055815:Young Adult
chemical_list: D001381:Azepines; D000068796:Orexin Receptor Antagonists; D014230:Triazoles; C551624:suvorexant; D000431:Ethanol
keywords: Alcohol; pharmacokinetics; pharmacology; psychomotor performance; suvorexant