Evaluation of equations for unbound serum concentration prediction of carbamazepine and carbamazepine-10,11-epoxide in polytherapy pediatric patients with epilepsy.

We retrospectively evaluated the ability of equations with in vivo population binding parameters of our previous study (Method 1) or an average unbound fraction of 0.25 of Pynnönen (Method 2) to predict the unbound serum carbamazepine (CBZ) concentration in 50 serum samples from 28 polytherapy pediatric patients with epilepsy. In 12 serum samples from 10 patients, the ability of equations for unbound serum carbamazepine-10,11-epoxide (CBZ-E) concentration prediction was also determined in predictive performance with in vivo population binding parameters of our previous study (Method A) or an average unbound fraction of 0.5 of Pynnönen (Method B). Mean prediction error, mean absolute prediction error (MAE), and root mean squared error (RMSE) were calculated for each method, and these values served as a measure of prediction bias and precision. Method 1 shows a bias to underpredict unbound serum CBZ. The MAE and RMSE were lower in Method 2 (MAE = 0.696 microM, RMSE = 0.912 microM) than in Method 1 (MAE = 0.946 microM, RMSE = 1.138 microM). Method 2 is superior to Method 1 in accuracy and precision. The effects of antiepileptic co-medications on predictive performance of Method 1 are relatively larger in a co-medicated group of serum samples with valproic acid (n = 33, MAE = 0.994 microM, RMSE = 1.211 microM) than in a group of serum samples without valproic acid co-medication (n = 17, MAE = 0.853 microM, RMSE = 0.979 microM).(ABSTRACT TRUNCATED AT 250 WORDS)