Chronic valproic acid and coantiepileptic drug therapy and incidence of increases in serum liver enzymes.

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 out-patients. The highest incidence (SGOT, 28.3%; SGPT, 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 less than 0.01), PB concentration (n = 86, r = 0.352, p less than 0.01), PHT concentration (n = 45, r = 0.336, p less than 0.01), sum of VPA-PB concentrations (n = 86, r = 0.440, p less than 0.001), and sum of VPA-PB-PHT concentrations (n = 45, r = 0.481, p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)