Human brain GABA levels rise rapidly after initiation of vigabatrin therapy.
OBJECTIVE
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.


BACKGROUND
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
A single oral dose of vigabatrin rapidly increased brain GABA without side effects. Once-a-day dosing should be as effective as divided doses.
Petroff
O A
OA
Department of Neurology, Yale University, New Haven, CT 06510, USA.
Rothman
D L
DL
Behar
K L
KL
Collins
T L
TL
Mattson
R H
RH
D000284:Administration, Oral; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism*; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000627:therapeutic use
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin