Inhibition of the enzyme, GABA-aminotransferase in human platelets by vigabatrin, a potential antiepileptic drug.
1. The effect of the new antiepileptic drug, vigabatrin (gamma-vinyl GABA), on the platelet enzyme, GABA-aminotransferase (GABA-T) was investigated in volunteers and patients. Platelets GABA-T activity was assayed using a radioenzymic method. 2. Three single oral doses of vigabatrin (1 g, 2 g and 4 g) were given to six healthy male volunteers in an open randomised cross over study and compared with a baseline period preceding the three treatments. 3. Significant inhibition of the platelet GABA-T was produced by treatment with all three doses and a dose-response relationship was demonstrated. The minimum enzyme activities after 1 g, 2 g and 4 g doses were 43%, 30% and 21% respectively compared with the control values. 4. A significant depression of enzyme activity occurred at 30 min after drug administration and the values remained below control values for 72 h post-dose, outlasting the presence of the drug itself in the plasma. 5. Eight patients with chronic refractory epilepsy were treated with vigabatrin for 6 weeks. After taking the 2 g daily dose for 1 week there was a marked reduction in platelet enzyme activity in all subjects but the enzyme inhibition produced by the 3 g dose was not significantly different from that produced by the 2 g dose, even after 4 weeks treatment with the larger dose. The mean enzyme activity was approximately 30% throughout the active treatment period. One week after stopping vigabatrin, the enzyme levels were not significantly different from the baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)
Rimmer
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E
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff.
Kongola
G
G
Richens
A
A
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000293:Adolescent; D000328:Adult; D000614:Aminocaproates / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D001792:Blood Platelets / Q000201:enzymology*; D004827:Epilepsy / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D020888:Vigabatrin
D000614:Aminocaproates; D000927:Anticonvulsants; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin