Influence of age and co-medication on the concentration and efficacy of valproic acid in Chinese epilepsy children

Valproic acid (VPA) was a classic antiepileptic drug for fifty years. However, individual variability of plasma drug concentration was obvious in epilepsy patients and few researches focused on the relationship between concentration and efficacy. Consequently, in this study, the correlation of VPA concentration and efficacy was analyzed according to the subgroups of age, gender, and co-medication in Chinese children. Children diagnosed by epilepsy with monitoring of VPA from April 1, 2014 to March 31, 2017 were recruited. Data on age, gender, diagnosis, dose, co-medication, and concentration of VPA was collected and analyzed according to the efficacy. Total of 486 concentration data was included in this study. Doses and plasma concentrations were significantly increased with age (P<0.001, P<0.001). After adjusted by dose, the uncontrolled elder children (12-18 years) showed higher concentration/dose (C/D) ratio than the controlled group (P=0.02). However, there were no differences between male and female. For polytherapy, the C/D ratio of uncontrolled-group was higher than that of controlled group (P=0.005), especially with levetiracetam (LEV) and topiramate (TPM) (P=0.028, P=0.048). Age could explain some of the inter-individual pharmacokinetic of VPA, however, gender was not related to the concentration or efficacy of VPA which suggested that concentration monitoring was indispensable to children. Low metabolism, especially in the combination of LEV and TPM, might associate with the resistance of VPA, which could be a new sight to explore the resistance of VPA.