title: 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)
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000927:Anticonvulsants / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007223:Infant; D008099:Liver / Q000201:enzymology*; D008297:Male; D010634:Phenobarbital / Q000009:adverse effects; D010672:Phenytoin / Q000009:adverse effects; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D010672:Phenytoin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010634:Phenobarbital