title: Altering ethanol pharmacokinetics to treat alcohol use disorder: Can you teach an old dog new tricks?
abstract: Disulfiram was the first pharmacotherapy approved to treat alcohol use disorder in the 1950s. Disulfiram alters ethanol pharmacokinetics and causes uncomfortable reactions (e.g. headache, tachycardia, nausea, flushing and hypotension) when alcohol is consumed. Subsequently, a better understanding of the neurobiological pathways involved in alcohol use disorder led to the development of other medications (e.g. naltrexone and acamprosate). These neurobiological-based medications act on alcohol use disorder-related phenotypes including craving, stress, and/or withdrawal. The original approach to treat alcohol use disorder, by altering ethanol pharmacokinetics has been much less investigated. Recent research on ethanol pharmacokinetics has shed light on the mechanisms of action underlying alcohol use disorder and how some medications that alter ethanol pharmacokinetics may be helpful in treating alcohol use disorder. This review summarizes and discusses the complex pharmacokinetics of ethanol, and proposes that altering ethanol pharmacokinetics via novel pharmacological approaches may be a viable approach to treat alcohol use disorder.
authors.affiliation: 1 Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA.|2 Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA.|3 Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Haass-Koffler
authors.affiliation: 4 Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Akhlaghi
authors.affiliation: 1 Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA.|5 Veterans Affairs Medical Center, Providence, RI, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Swift
authors.affiliation: 2 Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA.|3 Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leggio
mesh_terms: D000437:Alcoholism / Q000188:drug therapy*; D000431:Ethanol / Q000493:pharmacokinetics*; D006801:Humans
chemical_list: D000431:Ethanol
keywords: Pharmacokinetics; alcohol use disorder; biobehavioral mechanisms; ethanol; human laboratory studies