PHARMACOKINETIC INTERACTION STUDIES BETWEEN FELBAMATE AND VIGABATRIN

To assess the possible occurrence of pharmacokinetic interactions betw een the antiepileptic agents felbamate and vigabatrin, two randomized, double-blind, placebo-controlled, crossover studies were conducted in healthy male volunteers. In Study I, 18 subjects received oral vigaba trin 1000 mg every 12 h for two 8 day periods with felbamate 1200 mg e very 12 h or placebo. In Study II, 18 other volunteers were administer ed oral felbamate 1200 mg every 12 h for two 8 day periods with vigaba trin 1000 mg every 12 h or placebo. On the eighth day of each treatmen t period, blood and urine samples were collected over 12 h for determi nation of the active S(+)- and inactive R(-)-vigabatrin enantiomer con centrations (Study I) or felbamate concentrations (Study II). In Study I, the pharmacokinetic parameters of R(-)-vigabatrin were similar dur ing co-administration with felbamate or placebo. Felbamate produced a 13% increase in AUC(0,12 h) and an 8% increase in urinary excretion of S(+)-vigabatrin. Although these changes were statistically significan t, their magnitude was small. In Study II, the pharmacokinetic paramet ers of felbamate were similar during concurrent administration with vi gabatrin or placebo. These data indicate that there are no clinically relevant pharmacokinetic interactions between felbamate and vigabatrin in man.