Evaluation of binding equation method for prediction of unbound serum valproic acid concentration in pediatric patients with epilepsy.

We retrospectively evaluated the ability of Scatchard binding equation method to predict the unbound serum valproic acid (VPA) concentration in 37 pediatric patients with epilepsy receiving VPA monotherapy. The correlation between predicted and observed unbound serum concentrations was high and significant (r = 0.873, p < 0.001). Mean prediction error (ME), mean absolute prediction error (MAE), and root mean squared error (RMSE) were calculated, and served as a measure of prediction bias and precision. The 95% confidence intervals of ME did not include 0, showing a bias to overpredict unbound concentration. The MAE and RMSE were not small in magnitude (MAE 17.4 mumol/l, RMSE 22.8 mumol/l). The current method using the in vivo population mean binding parameters from healthy young adults may be limited in the predictive performance of unbound serum VPA concentration.