Abstract
Suvorexant is an orexin receptor antagonist indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. As suvorexant is metabolized primarily by Cytochrome P450 3A (CYP3A), and its pharmacokinetics may be affected by CYP3A modulators, the effects of CYP3A inhibitors (ketoconazole or diltiazem) or an inducer (rifampin [rifampicin]) on the pharmacokinetics, safety, and tolerability of suvorexant were investigated. In two Phase I, open-label, fixed-sequence trials (Studies P008 and P038), healthy subjects received a single oral dose of suvorexant followed by co-administration with multiple once-daily doses of strong/moderate CYP3A inhibitors (ketoconazole/diltiazem) or a strong CYP3A inducer (rifampin). Treatments were administered in the morning: suvorexant 4 mg with ketoconazole 400 mg (Study P008; N = 10), suvorexant 20 mg with diltiazem 240 mg (Study P038; N = 20), and suvorexant 40 mg with rifampin 600 mg (Study P038; N = 10). Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞), maximum plasma concentration (Cmax), half-life (t½), and time to Cmax (tmax) were derived from plasma concentrations of suvorexant collected at prespecified time poi...Continue Reading
References
Dec 1, 1994·Clinical Pharmacology and Therapeutics·A VarheP J Neuvonen
May 1, 1994·Clinical Pharmacology and Therapeutics·K T OlkkolaP J Neuvonen
Jan 1, 1996·Clinical Pharmacology and Therapeutics·J T BackmanP J Neuvonen
Jan 1, 1997·Clinical Pharmacology and Therapeutics·K VillikkaP J Neuvonen
Jan 20, 1998·Clinical Pharmacology and Therapeutics·K VillikkaP J Neuvonen
Mar 10, 1998·Cell·T SakuraiM Yanagisawa
Oct 3, 1998·Clinical Pharmacology and Therapeutics·D J GreenblattR I Shader
Dec 13, 1976·Drug Information Journal·L Fleckenstein
Oct 31, 2001·The European Journal of Neuroscience·Y YoshidaS Nishino
Jul 29, 2003·Clinical Pharmacokinetics·Mikko NiemiKari T Kivistö
Aug 5, 2008·Current Topics in Medicinal Chemistry·Anthony J Roecker, Paul J Coleman
Feb 28, 2009·Journal of Clinical Pharmacology·S A StochJ A Wagner
Nov 3, 2010·Annual Review of Pharmacology and Toxicology·Thomas E Scammell, Christopher J Winrow
Jan 7, 2011·Journal of Clinical Pharmacology·Evan J FriedmanS Aubrey Stoch
May 17, 2011·Vaccine·Christoph HatzChristian Herzog
Jul 5, 2012·Pharmacological Reviews·Anthony L GotterChristopher J Winrow
Dec 1, 2012·Neurology·W Joseph HerringDavid Michelson
Jun 5, 2013·British Journal of Pharmacology·C J Winrow, J J Renger
Apr 1, 2014·Lancet Neurology·David MichelsonW Joseph Herring
Dec 21, 2014·Biological Psychiatry·W Joseph HerringDavid Michelson
Sep 8, 2015·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·S A BreidingerE J Woolf
Feb 13, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Donghui CuiThomayant Prueksaritanont
Nov 20, 2016·Annual Review of Pharmacology and Toxicology·Paul J ColemanJohn J Renger
Apr 22, 2017·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·W Joseph HerringDavid Michelson
May 19, 2017·Journal of Child and Adolescent Psychopharmacology·Kentaro KawabeYasunori Oka
May 1, 2018·Clinical Drug Investigation·Ka Lai YeeRebecca E Wrishko