VALPROATE AND CARBAMAZEPINE COMEDICATION CHANGES HEPATIC ENZYME-ACTIVITIES IN SERA OF EPILEPTIC CHILDREN

Previous observation that valproic acid (VPA) and carbamazepine (CBZ) caused hepatic damage prompted us to investigate the effects of VPA or CBZ monotherapy and VPA + CBZ comedication on the number of hepatic e nzyme activities in sera of epileptic children. This study compares al anine aminotransferase (ALT), aspartate aminotransferase (AST) and gam ma-glutamyltransferase (GGT) activities in sera of children treated wi th VPA (n = 42), or CBZ (n = 36) taken as a monotherapy, with VPA + CB Z combined therapy (n = 36). The effect of VPA alone is greater on the activity of AST than on other enzymes, while CBZ therapy changes prim arily the activities of GGT. The mean catalytic activity of AST was si gnificantly elevated in groups on VPA, CBZ and VPA + CBZ treatment (2. 02-, 1.49- and 1.45-fold increase, respectively) as compared to the co ntrol values. Changes in the ALT activity followed different patterns. The maximal increase was observed in the CBZ group with a smaller inc rease in the group on VPA + CBZ polytherapy, whereas only 15% of patie nts receiving VPA showed an average 1.38-fold increase of the mean enz yme activity. Increase in the catalytic activity of GGT probably refle cts the induction produced by the CBZ treatment, either alone or in co mbination. Children on CBZ monotherapy showed an increase of mean cata lytic activity of about twofold in 56% of patients. Children on VPA CBZ comedication showed a similar behaviour, while VPA alone produced a moderate (1.44-fold) increase in 23% of children. However, concentra tions of VPA and CBZ in sera of patients receiving monotherapy were wi thin the expected therapeutic limits, whereas subtherapeutic levels of VPA were found in 30% of children on VPA + CBZ comedication. We propo se that individual dosage adjustment in VPA + CBZ polytherapy should b e combined with monitoring of relevant enzyme activities in serum. (C) 1998 Elsevier Science B.V. All rights reserved.