Butanediol conversion to gamma-hydroxybutyrate markedly reduced by the alcohol dehydrogenase blocker fomepizole.

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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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)

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:

Christine Baumgartner

Date Deposited:

30 Jan 2019 16:27

Last Modified:

01 Dec 2019 02:31

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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