Chronic Valproic Acid and Coantiepileptic Drug Therapy and Incidence of Increases in Serum Liver Enzymes

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Abstract
Results are described on the association of increased serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) activities with valproic acid (VPA) and coantiepileptic drug therapy in a group (n = 126) of randomly selected chronically medicated outpatients. The highest incidence (SGOT, 28.3%; SGOT, 26.1%) of elevations occurred in patients comedicated with VPA-phenobarbital (PB)-phenytoin (PHT) combinations, followed by those in the VPA-PB group (SGOT, 19.5%; SGPT, 7.3%). No SGPT elevations were detected in any patients (n = 40) on chronic VPA monotherapy, while SGOT was marginally elevated in 20% of the cases. Considering the total sample (n = 126), SGOT activities were found to be linearly and directly correlated with VPA plasma concentration (n = 126, r = 0.228, p < 0.01). PB concentration (n = 86, r = 0.352, p < 0.01), PHT concentration (n = 45, r = 0.336, p < 0.01), sum of VPA-PB concentrations (n = 86, r = 0.440, p < 0.001), and sum of VPA-PB-PHT concentrations (n = 45, r = 0.481, p < 0.001). The corresponding correlations for SGPT activities were similar, except that no correlation was observed in the case of VPA monotherapy. Student''s t tests for equality of means showed that the subgroup with abnormal enzyme activities had a significantly higher mean plasma concentration for PB, PHT, sum of VPA-PB, and sum of VPA-PB-PHT when compared with normal enzyme subgroup patients. Furthermore, linear regression analyses of the abnormal enzyme activities and antiepileptic drug concentration produced direct significant correlation in the case of SGOT with sum of VPA-PB concentrations (n = 20, r = 0.587, p < 0.01), and with sum of VPA-PB-PHT concentrations (n = 12, r = 0.592, p < 0.025). Patients on VPA and coantiepileptic drug therapy (PB and PHT) are the most likely group to show abnormal SGOT and SGPT activities. None of the patients had SGOT activities higher than twice the upper limit of normal or SGPT activities higher than thrice. Such mild elevations do not appear to be clinically significant and are probably due to enzyme induction.

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