Plasma vigabatrin enantiomer ratios in adults and children.
The new anticonvulsant vigabatrin (gamma-vinyl-gamma-aminobutyric acid) is normally supplied as a racemate, but its anticonvulsant effect is thought to reside in its [S]-enantiomer only. The plasma concentration ratio of the [R] to [S] enantiomers appears to remain constant across the vigabatrin dosage interval in adult volunteers, and in the present study this has also proved to be the case in 12 chronically treated adult epileptic patients. However, in 8 epileptic children chronically treated with other anticonvulsants and given add-on vigabatrin therapy because of failure to control seizures, plasma [R]:[S]-vigabatrin ratios changed across the drug dosage interval, the [R]-vigabatrin levels tending to be relatively higher soon after intake, and to fall more rapidly than the [S]-vigabatrin concentrations over the next few hours (mean half-lives 2.52 +/- SD 0.49 and 6.53 +/- SD 6.62 hours). The reason for the shorter half-life of [R]-vigabatrin in children remains to be elucidated, but it appears that measurement of racemic vigabatrin plasma concentrations in children, though not in adults, may lead to somewhat misleading conclusions as regards the amount of the circulating anticonvulsant [S]-vigabatrin.
Nagarajan
L
L
Department of Neurology, Royal Children's Hospital, Brisbane.
Schramm
T
T
Appleton
D B
DB
Burke
C J
CJ
Eadie
M J
MJ
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood; D000927:Anticonvulsants / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002849:Chromatography, Gas / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D013237:Stereoisomerism; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin