Dose-dependent pharmacokinetics and hypnotic effects of sodium gamma-hydroxybutyrate in the rat.

The pharmacokinetics of sodium-gamma-hydroxybutyrate (NaGHB) have been examined as functions of dose and route of administration. The elimination of NaGHB appeared to be controlled by a capacity-limited process which can be described by Michaelis-Menten kinetics. Oral absorption of NaGHB appeared to be fairly extensive in the dose range studied (200-1600 mg/kg), but the peak drug plasma concentrations achieved after oral dosing were relatively low and insensitive to changes in the magnitude of the dose, explaining the lack of pharmacological activity, viz., hypnosis, after oral NaGHB administration even at comparatively high doses. Plasma and brain concentrations were determined at the time when the animals recovered from the hypnotic effects of NaGHB. These concentrations also appeared to be dose-dependent, although the ratio of "waking" plasma to brain concentration was constant with respect to dose.