Gamma-vinyl GABA (vigabatrin): relationship between dosage, plasma concentrations, platelet GABA-transaminase inhibition, and seizure reduction in epileptic children.
The relationship between vigabatrin gamma-vinyl GABA (GVG, vigabatrin) daily dosage or steady-state plasma concentrations (CSS), platelet GABA-transaminase (GABA-T) inhibition, and seizure reduction were studied in 16 children with refractory epilepsy. After 2 months of observation and 1 month of single-blind add-on placebo, a fixed GVG dosage was added for 2 months. The dosage was then adjusted in two 2-month periods each, based on the patient's clinical response. In the fixed-dose period, GVG dosages of 56.8 mg/kg/day and CSS of 8.1 mg/L reduced GABA-T activity from 13.9 to 5.1 pmol/min/mg protein (p less than 0.001) and that of seizures from 51.4 to 22.3 seizures per month (p less than 0.01). Seizure reduction was correlated with dosage (r = 0.83, p less than 0.001), but not with CSS or with platelet GABA-T inhibition. After the GVG dose-adjustment periods, in which dosages of 84.4 mg/kg/day and CSS of 10.6 mg/L were reached, only a slight reduction was observed in both GABA-T activity (from 5.1 to 4.9 pmol/min/mg protein) and seizures (from 22.3 to 18.1 seizures per month). In GVG-responsive patients (excluding placebo-sensitive and GVG-resistant patients), a greater reduction of seizures was achieved (from 17.0 to 7.1 seizures per month, p less than 0.05), which was not accompanied by greater inhibition of GABA-T. GVG treatment in children should be started with a dosage of 50 mg/kg/day, increased to 75 or even 100 mg/kg/day when a partial response is observed. If seizures do not improve or if they become worse, the patient should be considered resistant and GVG should be discontinued.
Arteaga
R
R
Neuropediatrics Service, M. de Valdecilla University Hospital, Faculty of Medicine, University of Cantabria, Santander, Spain.
Herranz
J L
JL
Valdizán
E M
EM
Armijo
J A
JA
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000293:Adolescent; D000367:Age Factors; D000614:Aminocaproates / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D001792:Blood Platelets / Q000201:enzymology; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D016037:Single-Blind Method; D020888:Vigabatrin
D000614:Aminocaproates; D000927:Anticonvulsants; D010919:Placebos; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin