HUMAN BRAIN GABA LEVELS RISE RAPIDLY AFTER INITIATION OF VIGABATRIN THERAPY

Objective: The purpose of this study was to measure changes in brain G ABA after a single oral dose (50 mg/kg) of vigabatrin in patients with intractable epilepsy. Background: Vigabatrin is a safe and effective antiepileptic medication designed to increase brain GABA by irreversib ly inhibiting GABA-transaminase. Serial measurements showed that brain GABA levels increased from 1.0 (SEM, 0.07) to 2.4 mmol/kg (SEM, 0.09) in patients who were regularly taking vigabatrin (50 mg/kg/day divide d into two doses). Methods: in vivo measurements of GABA in human brai n were made using H-1 magnetic resonance spectroscopy. We used a 2.1-T NMR spectrometer and an 8-cm surface coil to measure a 13.5-cm(3) vol ume in the occipital cortex. Results: Brain GABA increased by more tha n 40% within 2 hours of administration of a single 50 mg/kg oral dose of vigabatrin from 0.95 (SEM, 0.07; n=7) to 1.34 mmol/kg (SEM, 0.13). By the next day, brain GABA increased further to 1.44 mmol/kg (SEM, 0. 08). Levels declined gradually to 1.16 mmol/kg (SEM, 0.14) by day 5 an d 1.03 mmol/kg (SEM, 0.10) at day 8. The patients reported no side eff ects and were calm but not drowsy. Conclusions: A single oral dose of vigabatrin rapidly increased brain GABA without side effects. Once-a-d ay dosing should be as effective as divided doses.