Activation of serum aminotransferases by pyridoxal-5′-phosphate in epileptic patients treated with anticonvulsant drugs

Objectives: Significant decreases in the serum concentration of pyridoxal-5′-phosphate (PLP) have been described in epileptic patients treated with anticonvulsant drugs. This would be expected to lead to a decrease in the sensitivity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) for the detection of hepatocellular damage in these patients if optimized methods with coenzyme supplementation are not used. The aim of our study was to evaluate this hypothesis. Design and Methods: The serum activities of AST and ALT (with and without the addition of PLP) were determined in a group of 90 adult epileptic patients (56 male, 34 female) undergoing chronic treatment polytherapy with phenobarbital, phenytoin, carbamazepine, and valproic acid. As a control group, 49 clinically healthy individuals were studied with a similar distribution for age and sex. Results: Supplementation with PLP produced an activation of AST and ALT in both the control and patient groups with a highly significant correlation between the enzyme activities with and without the addition of PLP (r ≥ 0.956, P< 0.001). The differences between the control and patient groups for the PLP activation of both aminotransferases were not clinically significant. The increases in AST (9%) and ALT (28%) in the patient group compared to the control group were lower than those found for alcohol dehydrogenase (ADH, 82%) and α-glutathione S-transferase (αGST, 76%). Conclusions: It does not appear that in the epileptic patients studied the in vitro addition of PLP increased the diagnostic sensitivity of AST and ALT for hepatocellular injury. The lower responses of both aminotransferases to the action of anticonvulsant drugs in relation to other cytosolic enzymes may be due to the preferred periportal localization of AST and ALT in the hepatic lobe.