Pharmacokinetics of the individual enantiomers of vigabatrin in neonates with uncontrolled seizures

Abstract

The antiepileptic drug vigabatrin (VGB) is a selective irreversible inhibitor of GABA-transaminase. It is administered as a racemic R(-), S(+) mixture, but the pharmacological activity of vigabatrin resides in the S(+) enantiomer and the R(-) enantiomer is inactive. The pharmacokinetic parameters of the two enantiomers have been studied after administration of a single oral 125 mg dose of the racemate to six neonates. The mean values of Cmax and AUC of the S(+) enantiomer were significantly lower (Cmax: 14.0 +/- 4.3 mg l-1; AUC: 143 +/- 44 mg l-1 h) than those of the R(-) enantiomer (Cmax: 34.1 +/- 9.5 mg l-1; AUC: 231 +/- 88 mg l-1 h), whereas no significant difference in the time to reach Cmax (S(+): 2.1 +/- 1.1 h; R(-): 2.2 +/- 1 h) was observed between the two enantiomers. During chronic administration (125 mg twice daily over 4 days), there was no evidence of accumulation of either enantiomer.