Pharmacokinetics of the individual enantiomers of vigabatrin (gamma-vinyl GABA) in epileptic children.
1. The pharmacokinetics of the enantiomers of vigabatrin were investigated after oral administration of a single 50 mg kg-1 dose of the racemate to two groups of six epileptic children (I: 5 months-2 years, II: 4-14 years). 2. The mean (+/- s.d.) values of maximum plasma concentration and area under the plasma concentration-time curve of the R(-) enantiomer were significantly higher than those of S(+) vigabatrin in both groups: R(-) Cmax: 21 +/- 6.6 (I)-41.3 +/- 13.9 (II) vs S(+) Cmax: 13.9 +/- 4.5 (I)-23.8 +/- 12.2 (II) mg l-1; R(-) AUC: 106 +/- 28.5 (I)-147 +/- 34 (II) vs S(+) AUC: 90.9 +/- 27.9 (I)-117 +/- 26 (II) mg l-1 h. In group I, the half-life of the R(-) isomer was significantly shorter than that of the S(+) isomer; in group II, the half-lives were comparable. 3. For the R(-) enantiomer the area under the curve, and the elimination half-life increased linearly with age. 4. During chronic administration (50 mg kg-1 vigabatrin racemate twice a day for 4 days), the morning trough plasma drug concentrations did not increase.
Département de Pharmacologie Périnatale et Pédiatrique, Hôpital Saint-Vincent de Paul, Paris, France.
E
E
Rey
G
G
Pons
M O
MO
Richard
F
F
Vauzelle
P
P
D'Athis
C
C
Chiron
O
O
Dulac
D
D
Beaumont
G
G
Olive
D000293:Adolescent; D000375:Aging / Q000378:metabolism; D000614:Aminocaproates / Q000493:pharmacokinetics* / Q000652:urine; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000652:urine; D002648:Child; D004827:Epilepsy / Q000188:drug therapy* / Q000652:urine; D006801:Humans; D007223:Infant; D013237:Stereoisomerism; D020888:Vigabatrin
D000614:Aminocaproates; D000927:Anticonvulsants; D020888:Vigabatrin