The effect of different vigabatrin treatment regimens on CSF biochemistry and seizure control in epileptic patients

摘要

>1 Vigabatrin, 50 mg kg^-1, was administered orally as add-on therapy to 11 patients with drug-resistant complex partial epilepsy as a single dose, then once every third day for 2 months, every other day for 2 months and daily for 1 month.>2 Lumbar punctures were carried out prior to treatment and at the end of each dosage regimen and cerebrospinal fluid (CSF) evaluated for concentrations of free and total GABA, homocarnosine (GABA-histidine dipeptide), homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA) and vigabatrin.>3 Each regimen resulted in significant increases in CSF concentrations of free and total GABA and homocarnosine compared with the immediately preceding regimen.>4 CSF concentrations of HVA significantly increased after a single vigabatrin dose but returned to pre-treatment levels with subsequent dosing schedules. In contrast, 5-HIAA concentrations also increased with the single dose but were significantly decreased, compared with pre-treatment values, following alternate day and daily vigabatrin administration.>5 Seizure frequency progressively decreased with decreasing dosing interval. Daily vigabatrin administration was associated with > 50% decrease in seizures in 8 of the 10 patients treated.