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Pharmacokinetics and pharmacodynamics of γ-hydroxybutyrate in healthy subjects

Liechti, Matthias E. and Quednow, Boris B. and Liakoni, Evangelia and Dornbierer, Dario and von Rotz, Robin and Salomé Gachet, M. and Gertsch, Jürg and Seifritz, Erich and Bosch, Oliver G.. (2016) Pharmacokinetics and pharmacodynamics of γ-hydroxybutyrate in healthy subjects. British Journal of Clinical Pharmacology, 81 (5). pp. 980-988.

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Abstract

γ-Hydroxybutyrate (GHB) is used as a treatment for narcolepsy and alcohol withdrawal and as recreational substance. Nevertheless, there are limited data on the pharmacokinetics and pharmacokinetic-pharmacodynamic relationship of GHB in humans. We characterized the pharmacokinetic profile and exposure-psychotropic effect relationship of GHB in humans.; Two oral doses of GHB (25 and 35 mg/kg) were administered to 32 healthy male subjects (16 for each dose) using a randomized, placebo-controlled, cross-over design.; Maximal concentrations of GHB were (geometric mean and 95%CI): 218 (176-270) nmol/ml and 453 (374-549) nmol/ml for the 25 and 35 mg/kg GHB doses, respectively. The elimination half-lives (mean ± SD) were 36 ± 9 and 39 ± 7 min and the AUC∞ values (geometric mean and 95%CI) were 15,747 (12,854-19,290) and 40,113 (33,093-48,622) nmol∙min/ml for the 20 and 35 mg/kg GHB doses, respectively. Thus, plasma GHB exposure (AUC0-∞ ) rose disproportionally (+40%) with the higher dose. γ-Hydroxybutyrate produced mixed stimulant-sedative effects, with a dose-dependent increase in sedation and dizziness. It did not alter heart rate or blood pressure. A close relationship between plasma GHB exposure and its psychotropic effects was found, with higher GHB concentrations associated with higher subjective stimulation, sedation, and dizziness. No clockwise hysteresis was observed in the GHB concentration effect plot over time (i.e., no acute pharmacological tolerance).; Evidence was found of a non-linear dose-exposure relationship (i.e., no dose proportionality) at moderate doses of GHB. The effects of GHB on consciousness were closely linked to its plasma exposure and exhibited no acute tolerance. This article is protected by copyright. All rights reserved.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Psychopharmacology Research (Liechti)
UniBasel Contributors:Liechti, Matthias Emanuel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:0306-5251
e-ISSN:1365-2125
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:26 May 2018 18:47
Deposited On:04 Dec 2017 11:06

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