Petroff O A, Rothman D L, Behar K L, Collins T L, Mattson R H
Department of Neurology, Yale University, New Haven, CT 06510, USA.
Neurology. 1996 Dec;47(6):1567-71. doi: 10.1212/wnl.47.6.1567.
The purpose of this study was to measure changes in brain GABA after a single oral dose (50 mg/kg) of vigabatrin in patients with intractable epilepsy.
Vigabatrin is a safe and effective antiepileptic medication designed to increase brain GABA by irreversibly 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 divided into two doses).
In vivo measurements of GABA in human brain were made using 1H magnetic resonance spectroscopy. We used a 2.1-T NMR spectrometer and an 8-cm surface coil to measure a 13.5 cm3 volume in the occipital cortex.
Brain GABA increased by more than 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 and 1.03 mmol/kg (SEM, 0.10) at day 8. The patients reported no side effects and were calm but not drowsy.
A single oral dose of vigabatrin rapidly increased brain GABA without side effects. Once-a-day dosing should be as effective as divided doses.
