Liakoni, Evangelia; Gugelmann, Hallam; Dempsey, Delia A; Wiegand, Timothy J; Havel, Christopher; Jacob, Peyton; Benowitz, Neal L (2019). Butanediol conversion to gamma-hydroxybutyrate markedly reduced by the alcohol dehydrogenase blocker fomepizole. Clinical pharmacology and therapeutics, 105(5), pp. 1196-1203. Wiley 10.1002/cpt.1306
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Liakoni_et_al-2019-Clinical_Pharmacology_&_Therapeutics.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (523kB) |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine |
UniBE Contributor: |
Liakoni, Evangelia |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1532-6535 |
Publisher: |
Wiley |
Language: |
English |
Submitter: |
Tobias Tritschler |
Date Deposited: |
30 Jan 2019 16:27 |
Last Modified: |
05 Dec 2022 15:24 |
Publisher DOI: |
10.1002/cpt.1306 |
PubMed ID: |
30450642 |
Uncontrolled Keywords: |
1 4-butanediol alcohol dehydrogenase fomepizole gamma-hydroxybutyrate |
BORIS DOI: |
10.7892/boris.123185 |
URI: |
https://boris.unibe.ch/id/eprint/123185 |
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