γ‐Vinyl GABA (Vigabatrin): Relationship Between Dosage, Plasma Concentrations, Platelet GABA‐Transaminase Inhibition, and Seizure Reduction in Epileptic Children

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Abstract
Summary: The relationship between vigabatrin γ‐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 < 0.001) and that of seizures from 51.4 to 22.3 seizures per month (p < 0.01). Seizure reduction was correlated with dosage (r= 0.83, p < 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 < 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.