Butanediol conversion to gamma-hydroxybutyrate markedly reduced by the alcohol dehydrogenase blocker fomepizole
Autor: | Neal L. Benowitz, Evangelia Liakoni, Christopher Havel, Timothy J. Wiegand, Delia A. Dempsey, Hallam Gugelmann, Peyton Jacob |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Adult
Male medicine.medical_specialty Mean arterial pressure Metabolic Clearance Rate Placebo Article Double-Blind Method Oral administration Internal medicine medicine Humans Pharmacology (medical) Enzyme Inhibitors Fomepizole 610 Medicine & health Butylene Glycols Alcohol dehydrogenase Pharmacology Psychotropic Drugs Cross-Over Studies biology Chemistry Alcohol Dehydrogenase Gamma hydroxybutyrate Crossover study Healthy Volunteers Endocrinology Treatment Outcome Butanediol biology.protein Solvents Drug Monitoring Sodium Oxybate medicine.drug |
Zdroj: | Clin Pharmacol Ther |
Popis: | 1,4-Butanediol (BDO) - used as solvent, and abused for its euphoric effects - is converted to gamma-hydroxybutyrate (GHB) by the enzyme alcohol dehydrogenase (ADH). This double-blind, placebo-controlled crossover study with six healthy volunteers is the first to date investigating the role of the ADH inhibitor fomepizole (4MP) in moderating this conversion in humans. Participants received on two different days either intravenous placebo or 15 mg/kg 4MP, followed by oral administration of 25 mg/kg BDO. Pretreatment with 4MP resulted in significantly higher BDO maximal plasma concentration (p=0.001) and AUC (p=0.028), confirming that ADH is the primary pathway for the conversion of BDO to GHB in humans. With 4MP, the mean arterial pressure was significantly lower at 105 minutes compared to baseline (p=0.003), indicating that blood pressure lowering, observed not with a temporal relationship to 4MP administration but after the maximum BDO concentration was reached, may be an intrinsic effect of BDO. This article is protected by copyright. All rights reserved. |
Databáze: | OpenAIRE |
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