title: Gamma-hydroxybutyrate (GHB) in humans: pharmacodynamics and pharmacokinetics.
abstract: Despite gamma-hydroxybutyrate (GHB) therapeutic uses and the increasing concern about its toxicity, few studies have addressed GHB dose-related effects under controlled administration and their relationship with its pharmacokinetics. The study design was double-blind, randomized, crossover, and controlled. As a pilot pharmacology phase I study, increasing doses of GHB were given. Single oral sodium GHB doses (40, 50, 60, and 72 mg/kg) were administered to eight volunteers. Plasma and urine were analyzed for GHB by gas chromatography-mass spectrometry. Physiological effects, psychomotor performance, and subjective effects were examined simultaneously. GHB produced dose-related changes in subjective effects as measured by questionnaires and VAS. GHB showed a mixed stimulant-sedative pattern, with initially increased scores in subjective feeling of euphoria, high, and liking followed by mild-moderate symptoms of sedation with impairment of performance and balance. Mean peak GHB plasma concentrations were 79.1, 83.1, 113.5, and 130.1 mug/L for 40, 50, 60, and 72 mg/kg, respectively. GHB-mediated physiological and subjective effects were dose dependent and related to GHB plasma concentrations. GHB urinary excretion was mainly related to administered doses. GHB-mediated subjective and physiological effects seem dose dependent and related to GHB plasma concentrations. Results suggest a high abuse liability of GHB in the range of dose usually consumed.
authors.affiliation: Pharmacology Research Unit, Human Pharmacology and Clinical Neurosciences Research Group, Institut Municipal d'Investigació Mèdica (IMIM), c/ Doctor Aiguader 80, 08003 Barcelona, Spain. sabanades@imim.es
authors.forename: Sergio
authors.initials: S
authors.lastname: Abanades
authors.forename: Magi
authors.initials: M
authors.lastname: Farré
authors.forename: Mireia
authors.initials: M
authors.lastname: Segura
authors.forename: Simona
authors.initials: S
authors.lastname: Pichini
authors.forename: Diego
authors.initials: D
authors.lastname: Barral
authors.forename: Roberta
authors.initials: R
authors.lastname: Pacifici
authors.forename: Manuela
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Francina
authors.initials: F
authors.lastname: Fonseca
authors.forename: Klaus
authors.initials: K
authors.lastname: Langohr
authors.forename: Rafael
authors.initials: R
authors.lastname: De La Torre
mesh_terms: D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011596:Psychomotor Disorders / Q000378:metabolism; D012978:Sodium Oxybate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019966:Substance-Related Disorders / Q000378:metabolism*; D013997:Time Factors
chemical_list: D012978:Sodium Oxybate