PHARMACOKINETICS OF VIGABATRIN FOLLOWING SINGLE AND MULTIPLE ORAL DOSES IN NORMAL VOLUNTEERS

The pharmacokinetics of vigabatrin were investigated after single and multiple oral doses in two groups of 24 healthy male volunteers. Vigab atrin was well tolerated by the volunteers, headache was the most freq uently reported adverse event. There were no clinically remarkable cha nges in serum chemistry, urinalysis, or hematology attributable to vig abatrin. For the single-dose study, a stepwise linear contrast method was used to assess dose proportionality. The results showed that vigab atrin exhibited dose linear pharmacokinetics after single oral doses r anging from 0.5 to 4.0 g. Slight changes in the terminal phase half-li fe and renal clearance were evident in the higher dosage groups. These changes with increasing dose of vigabatrin were relatively minor and not considered to be clinically important. Evaluation of the multiple- dose pharmacokinetics indicated that vigabatrin exhibited dose lineari ty over the range of 0.5 to 2.0 g administered every 12 hours. The ter minal phase half-life and renal clearance of vigabatrin during multipl e dosing were consistent with that after single doses. During multiple dosing, steady-state concentrations of vigabatrin were reached on the second day of dosing, and drug accumulation was minimal.