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Pharmacokinetics of the individual enantiomers of vigabatrin in neonates with uncontrolled seizures
Author(s) -
VAUZELLEKERVROËDAN F.,
REY E.,
PONS G.,
D'ATHIS Ph.,
CHIRON C.,
DULAC O.,
DUMAS C.,
OLIVE G.
Publication year - 1996
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1996.00495.x
Subject(s) - vigabatrin , enantiomer , pharmacokinetics , pharmacology , oral administration , gaba transaminase , chemistry , anticonvulsant , medicine , epilepsy , stereochemistry , biochemistry , enzyme , psychiatry , glutamate decarboxylase
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 C max and AUC of the S(+) enantiomer were significantly lower ( C max : 14.0±4.3 mg l −1 ; AUC: 143±44 mg l −1 h) than those of the R(−) enantiomer ( C max : 34.1±9.5 mg l −1 ; AUC: 231±88 mg l −1 h), whereas no significant difference in the time to reach C max (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.