DOSE-DEPENDENT ABSORPTION AND ELIMINATION OF GAMMA-HYDROXYBUTYRIC ACID IN HEALTHY-VOLUNTEERS

Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcoh ol and opiate withdrawal syndromes. Its absorption and disposition kin etics have been studied in 8 healthy male volunteers following oral ad ministration of single doses of 12.5, 25 and 50 mg kg-1. The AUC incre ased disproportionately with the dose and so the apparent oral clearan ce decreased significantly as the dose was increased, whereas the term inal half-life and mean residence time increased. The peak plasma conc entrations normalised to the lowest dose fell significantly with incre asing doses, whilst the corresponding peak times increased. These find ings 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 phar macokinetic parameters in healthy volunteers were not significantly di fferent from those previously observed in alcohol-dependent patients w ith compensated alcoholic liver disease.