Prediction of Unbound Serum Valproic Acid Concentration by Using In Vivo Binding Parameters

In a previous study, we determined the in vivo binding parameters of valproic acid (VPA) to serum proteins in seven healthy young adults at steady state by using the Scatchard equation. To evaluate the ability of the Scatchard binding equation to predict steady-state unbound serum VPA concentrations (Cf), 39 adult patients receiving VPA monotherapy and ranging in age from 16 to 68 years were studied. The correlation between predicted and observed Cf was high (r = 0.865). Mean prediction error, mean absolute error (MAE), and root mean squared error (RMSE) were calculated, and served as a measure of prediction bias and precision. The MAE and RMSE were low (MAE = 12.9 μmol/L, RMSE = 17.7 μmol/L). It is feasible to use the Scatchard binding equation to predict Cf in patients receiving VPA monotherapy.