Pharmacokinetics of the gamma-aminobutyric acid agonist THIP (Gaboxadol) following intramuscular administration to man, with observations in dog.

The pharmacokinetics of the gamma-aminobutyric acid (GABA) agonist, THIP (Gaboxadol) has been studied following intramuscular administration of 10 or 20 mg THIP-monohydrate to six healthy human volunteers. Additional experiments with special reference to the possible occurrence of non-linear kinetics and to estimation of the efficiency of absorption were carried out in three beagle dogs. As estimated from the dogs, absorption of THIP from the site of injection was efficient (F = 0.94 +/- 0.16, mean +/- S.D., in 8 experiments). The time course of the THIP serum concentration was in all experiments adequately described by an open 1-compartment linear model. In most individual experiments a near maximum concentration was present at 15 or 10 min. after the administration to man and dog, respectively. In some subjects and dogs an uncertain relation was found between dose and the time integral of the THIP serum concentration, but the mode of variation did not suggest deviations from first-order kinetics at high doses or concentrations. The rate constant of elimination was estimated to 0.50 +/- 0.13 hr-1 and 0.52 +/- 0.13 hr-1 following injection of a 10 or 20 mg dose, respectively, to man (mean +/- S.D., n = 6), and similar values were obtained from the dogs.