Valproic acid concentration and biochemical indexes in epilepsy outpatients during monotherapy or combination therapy

Due to the narrow therapeutic window of valproic acid (VPA), grievous adverse reactions such as hepatotoxicity, nephrotoxicity may occur in patients with epilepsy for a long time. This study aimed to explore the effect of VPA concentration on biochemical and routine blood test related to liver, renal, and hematology in epileptic outpatients treated with VPA alone or combined with other antiepileptic drugs.

A total of 3 194 Chinese epileptic outpatients from Xiangya Hospital, were analyzed in a crude analysis after stratifying through dosage regimens. The plasma VPA concentration was detected by gas chromatography method and then standardized through dosage and body weight. Ten biochemical indexes related to liver, renal, and hematology were evaluated.

Of all patients, blood urea nitrogen (BUN), serum creatinine (SCr) level, and erythrocyte count (RBC) showed positive correlations with standardized VPA concentration (r=0.494, r=0.157, r=0.596, respectively), while platelet specific volume (PCT) and blood platelet (PLT) showed negative correlations with standardized VPA concentration (r=-5.500, r=-0.086, respectively). After stratifying through dosage regimens, significantly positive associations between SCr and standardized VPA concentration were found in the juvenile patients from the monotherapy group and combination therapy group (r=1.800, r=0.352, respectively). In addition, PLT and leukocyte count (WBC) in the juvenile patients from the combination therapy group were negatively correlated with standardized VPA concentration (r=-1.463, r=-0.079, respectively), while RBC showed a positive association with standardized VPA concentration in the juvenile patients from the monotherapy group (r=0.068).

SCr level is significantly associated with plasma VPA concentration. Drug combination and age are important factors leading to hematological disorders. The finding provides potential theoretical guidance for the rational and safe clinical use of VPA.