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Evidence for both in vivo and in vitro interaction between vigabatrin and alanine transaminase
A Richens1, J R McEwan, J C Deybach
1Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Health Park, Cardiff, UK.
Aims:
Decreases in plasma alanine transaminase (ALA-T) activity of 20-100% have been reported following the use of vigabatrin (Sabril) in patients with uncontrolled epilepsy. This effect has a potential clinical significance as it may mask signs of early, underlying hepatic disease. It is particularly significant in a patient population known to have a higher than average risk of hepatotoxicity due to treatment with other anti-epilepsy drugs or to an independent, but concomitant, disease process. Vigabatrin is a highly specific enzyme antagonist. There is an almost 1000-fold difference between its activity against gamma-amino butyric acid aminotransaminase and ALA-T. However, some activity against other transaminases is not unexpected, and it, is important to determine the degree of vigabatrin's effect against ALA-T in man.
Methods:
Two in vitro experiments, using serum samples spiked with vigabatrin, confirmed the presence of an interaction between vigabatrin and ALA-T, and formed the basis for the design of a study in five healthy male volunteers, in whom serum ALA-T activity was measured before and after a single dose of 1.5 g of vigabatrin.
Results:
Serial sampling confirmed the presence of an in vivo interaction between vigabatrin and ALA-T, causing an inhibition of enzyme activity of 30-40%. A further 20% reduction was found in vitro in samples taken at the time of the peak plasma vigabatrin concentration after they had been stored for 6 h.
Conclusions:
The clinical significance of these findings is that the levels of ALA-T activity determined in patients receiving vigabatrin may be inaccurate. The "real' values must be assumed to be higher than those reported after routine testing. To obtain the most relistic measurement of ALA-T activity in patiets, samples should be taken at the times of trough plasma concentration and processed as soon as possible afterwards. Samples stored for any length of time at or above room temperature may also give even more false results.