Isoforms of serum gamma-glutamyltransferase in epileptic patients treated with enzyme-inducing anticonvulsant drugs.

Purpose: The increase of serum activity of gamma-glutamyltranferase (gammaGT) through the action of enzyme-inducing anticonvulsant drugs has been widely documented; however, the behaviour of its multiple forms and its relationship with the degree of enzyme induction has received little coverage. This subject is the major aim of our paper.

Methods: An electrophoretic study of the serum gammaGT isoforms was made in 90 adult epileptic patients under chronic treatment with phenobarbital, phenytoin and carbamazepine in polytherapy.

Results: A significant correlation was found (p<0.001) between the drug score and urinary excretion of D-glucaric acid (DGA) (r=0.773), total gammaGT (r=0.382), gammaGT1 (r=0.398) and gammaGT2 (r=0.361). In a group of 11 patients with the gammaGT3 isoforms, considered a sensitive test for cholestasis, serum activities of total gammaGT, gammaGT1, gammaGT2 and 5 -nucleotidase were found that were significantly higher than in the 79 patients without the gammaGT3 isoform (p<0.001); however, for the drug score and excretion of DGA, no significant differences were found, suggesting a similar degree of enzyme induction in both groups of patients.

Conclusions: The presence of cholestasis, at least biochemically detectable in some of these patients, appears to be a factor of paramount importance when interpreting the effect of enzyme-inducing anticonvulsant drugs on serum gammaGT. This fact may contribute towards explaining its highly varied response to the administration of these drugs.