{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:37:47Z","timestamp":1783402667330,"version":"3.54.6"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,2,25]],"date-time":"2016-02-25T00:00:00Z","timestamp":1456358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>\u03b3\u2010Hydroxybutyrate (GHB) is used as a treatment for narcolepsy and alcohol withdrawal and as a recreational substance. Nevertheless, there are limited data on the pharmacokinetics and pharmacokinetic\u2010pharmacodynamic relationships of GHB in humans. We characterized the pharmacokinetic profile and exposure\u2010psychotropic effect relationship of GHB in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two oral doses of GHB (25 and 35\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>) were administered to 32 healthy male subjects (16 for each dose) using a randomized, placebo\u2010controlled, cross\u2010over design.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Maximal concentrations of GHB were (geometric mean and 95% CI): 218 (176\u2013270) nmol\u00a0ml<jats:sup>\u22121<\/jats:sup> and 453 (374\u2013549) nmol\u00a0ml<jats:sup>\u22121<\/jats:sup> for the 25 and 35\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup> GHB doses, respectively. The elimination half\u2010lives (mean\u00a0\u00b1\u00a0SD) were 36\u00a0\u00b1\u00a09 and 39\u00a0\u00b1\u00a07\u00a0min and the AUC<jats:sub>\u221e<\/jats:sub> values (geometric mean and 95% CI) were 15\u00a0747 (12\u00a0854\u201319\u00a0290) and 40\u00a0113 (33\u00a0093\u201348\u00a0622) nmol\u2219min\u00a0ml<jats:sup>\u22121<\/jats:sup> for the 20 and 35\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup> GHB doses, respectively. Thus, plasma GHB exposure (AUC<jats:sub>0\u2010\u221e<\/jats:sub>) rose disproportionally (+40%) with the higher dose. \u03b3\u2010Hydroxybutyrate produced mixed stimulant\u2010sedative effects, with a dose\u2010dependent 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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Evidence was found of a nonlinear dose\u2010exposure 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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12863","type":"journal-article","created":{"date-parts":[[2015,12,11]],"date-time":"2015-12-11T15:54:30Z","timestamp":1449849270000},"page":"980-988","source":"Crossref","is-referenced-by-count":56,"title":["Pharmacokinetics and pharmacodynamics of \u03b3\u2010hydroxybutyrate in healthy subjects"],"prefix":"10.1111","volume":"81","author":[{"given":"Matthias E.","family":"Liechti","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research University Hospital Basel  \u0392asel CH\u20104031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris B.","family":"Quednow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital University of Zurich  Lenggstrasse 31 Zurich CH\u20108032 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Liakoni","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research University Hospital Basel  \u0392asel CH\u20104031 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Dornbierer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital University of Zurich  Lenggstrasse 31 Zurich CH\u20108032 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"von Rotz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital University of Zurich  Lenggstrasse 31 Zurich CH\u20108032 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Salom\u00e9","family":"Gachet","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine University of Bern  B\u00fchlstrasse 28 Bern CH\u20103012 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrg","family":"Gertsch","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine University of Bern  B\u00fchlstrasse 28 Bern CH\u20103012 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Seifritz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital University of Zurich  Lenggstrasse 31 Zurich CH\u20108032 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver G.","family":"Bosch","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, 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