Pharmacokinetics of gamma‐hydroxybutyric acid in alcohol dependent patients after single and repeated oral doses.

Abstract

1. The pharmacokinetics of gamma‐hydroxybutyric acid (GHB) were studied in 10 alcohol dependent subjects after single and repeated therapeutic oral doses (25 mg kg‐1 every 12 h for 7 days). 2. GHB was readily absorbed and rapidly eliminated (tmax = 20‐45 min; mean t1/2z 27 +/‐ 5 s.d. min). Urinary recovery of unchanged GHB was negligible (less than 1% of the dose). gamma‐butyrolactone was not detected in either plasma or urine, indicating that lactonization of GHB does not occur in vivo. 3. The multiple‐dose regimen resulted neither in accumulation of GHB nor in time‐dependent modification of its pharmacokinetics. 4. In five subjects, the data were consistent with nonlinear elimination kinetics of GHB. Administration of a 50 mg kg‐1 dose to these subjects resulted in significant increases in dose‐normalized AUC, t1/2z and mean residence time. 5. Doubling of the dose also resulted in a significant increase in tmax with little change in Cmax. 6. At the administered doses, GHB did not accumulate in the plasma and caused no serious side effects. 1992 The British Pharmacological Society