Visual field constriction: accumulation of vigabatrin but not tiagabine in the retina.
BACKGROUND
The antiepileptic drug (AED) vigabatrin (VGB) causes concentric visual field constriction. Anecdotal reports involving tiagabine (TGB) have implied that this may be a class effect of all AEDs with gamma-aminobutyric acid (GABA)-related actions. We investigated the pharmacokinetic and pharmacodynamic profiles of VGB and TGB in rat brain and eye.


METHODS
Adult male rats (n = 8) were administered 0.9% saline (control), VGB (500 or 1,000 mg/kg), or TGB (5, 10, or 20 mg/kg). At 1 (TGB) and 4 hours (VGB) postdosing, the animals were killed, a blood sample was obtained, their brains were dissected into five anatomic regions, and the retina and vitreous humor were isolated from each eye. Samples were analyzed for GABA concentrations and the activity of the enzyme GABA-transaminase (GABA-T). Plasma and tissue drug concentrations were also determined.


RESULTS
VGB treatment produced a decrease in the activity of GABA-T and a rise in GABA concentrations in all tissues investigated. This effect was most pronounced in the retina. VGB concentrations were as much as fivefold higher in the retina than in the brain. TGB was without effect on GABA concentrations and activity of GABA-T. TGB concentrations were notably lower in the retina than in the brain.


CONCLUSIONS
Accumulation of VGB in the retina, with or without an increase in GABA, may be responsible for the visual field constriction reported clinically. In contrast, TGB had no effect on GABA concentrations and did not accumulate in the retina. These results suggest that TGB is unlikely to cause visual field defects in humans.
Sills
G J
GJ
Epilepsy Unit, University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland. g.j.sills@clinmed.gla.ac.uk
Patsalos
P N
PN
Butler
E
E
Forrest
G
G
Ratnaraj
N
N
Brodie
M J
MJ
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D008297:Male; D009557:Nipecotic Acids / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects*; D000078308:Tiagabine; D020888:Vigabatrin / Q000009:adverse effects*; D014786:Vision Disorders / Q000139:chemically induced*; D014794:Visual Fields / Q000187:drug effects*
D000927:Anticonvulsants; D009557:Nipecotic Acids; D020888:Vigabatrin; D000078308:Tiagabine