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Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers (1993)

Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers (1993)

  1. Bajeda
    European Journal of Clinical Pharmacology 1993;45(4):353-6

    Palatini P (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Tedeschi L (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Frison G (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Padrini R (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Zordan R (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Orlando R (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Gallimberti L (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Gessa GL (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Ferrara SD (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).

    Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg-1. The AUC increased disproportionately with the dose and so the apparent oral clearance decreased significantly as the dose was increased, whereas the terminal half-life and mean residence time increased. The peak plasma concentrations normalised to the lowest dose fell significantly with increasing doses, whilst the corresponding peak times increased. These findings suggest that both the oral absorption and the elimination of GHB are capacity-limited processes. GHB did not bind to significant extent to plasma proteins over the therapeutic concentration range. The pharmacokinetic parameters in healthy volunteers were not significantly different from those previously observed in alcohol-dependent patients with compensated alcoholic liver disease.