Pharmacokinetic studies of AD-810, a new antiepileptic compound. Phase I trials.

: Pharmacokinetics of 3-sulfamoylmethyl-1,2-benzisoxazole (AD-810), a new possible antiepileptic compound, were evaluated in Phase I trials in nine healthy male volunteers. The subjects, divided into three groups, were given single oral dose of 200 mg (Group A), and oral doses of 200 mg/d (B) and 400 mg/d (C) for two d, respectively. AD-810 was well tolerated by all subjects. No neurologic side effects were observed. Evaluation of the laboratory screening profiles (hematological and biochemical examination) showed no clinically significant abnormalities. Mean peak plasma concentrations of AD-810 at 5.3-6.0 h after intake were 2.9, 5.1 and 13.0 micrograms/ml in Group A, B and C, respectively, and mean elimination half-life was about 60 h. Mean concentrations of AD-810 in erythrocytes were higher than those in plasma. The unchanged AD-810 and a major metabolite, the glucuronide of the N-O cleft compound, were excreted at 48.7% and 12.4% of the given dose in the urine for 2 weeks in Group C, respectively. The results suggest that AD-810 would induce no severe adverse effects in man at plasma concentrations over 10 micrograms/ml, the therapeutic concentrations predicted from animal experiments.