PHARMACOKINETICS OF GAMMA-HYDROXYBUTYRIC ACID IN ALCOHOL DEPENDENT PATIENTS AFTER SINGLE AND REPEATED ORAL DOSES

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 (t(max) = 20-45 min; mean t1/2Z 27 +/- 5 s.d. min). Urinary recovery of unchanged GHB was negligible (< 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 t(max) with little change in C(max). 6 At the administered doses, GHB did not accumulate in the plasma and caused no serious side effects.