Premium
Inhibition of the enzyme, GABA‐aminotransferase in human platelets by vigabatrin, a potential antiepileptic drug.
Author(s) -
Rimmer E,
Kongola G,
Richens A
Publication year - 1988
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1988.tb03298.x
Subject(s) - vigabatrin , anticonvulsant , platelet , enzyme , pharmacology , enzyme assay , enzyme inhibitor , epilepsy , medicine , endocrinology , chemistry , biochemistry , psychiatry
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)