Original Articles: PDF OnlyEVALUATION OF UNBOUND SERUM CARBAMAZEPINE AND CARBAMAZEPINE-10,11-EPOXIDE CONCENTRATION PREDICTION METHODS IN POLYTHERAPY ADULT PATIENTS WITH EPILEPSYKodama, Yasuo1*; Kuranari, Masae1; Fujii, Isao2; Kodama, Hirofumi3; Takeyama, Masaharu1Author Information 1 Departments of Clinical Pharmacy and 2 Neuropsychiatry, Oita Medical University, Oita, Japan. 3 Department of Clinical Pharmacy, Miyazaki Medical College, Miyazaki, Japan. * Address for correspondence: Department of Clinical Pharmacy, Oita Medical University, Hasama-machi, Oita, 879–55, Japan. American Journal of Therapeutics: October 1996 - Volume 3 - Issue 10 - p 699-707 Buy Abstract 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 35 serum samples from 18 adult patients with epilepsy receiving polytherapy. In 9 serum samples from 6 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 smaller in Method 2 (MAE = 0.454 μm/L, RMSE = 0.597 μm/L than Method 1 (MAE = 0.597 μm/L, RMSE = 0.721 μm/L). Method 2 is superior to Method 1 in accuracy and precision. The effects of antiepileptic comedications on predictive performance of Methods 1 and 2 were determined in each group of serum samples with (n = 18, Group 1) or without (n = 17, Group 2) valproic acid (VPA) comedication. The results obtained by Method 1 show a bias to underprediction in Group 1 and no bias to over- or underprediction in Group 2. Results obtained by Method 2 show no bias to over- or underprediction in Groups 1 and 2. The effects of VPA comedication on predictive performance of unbound serum CBZ are relatively larger in Method 1 than Method 2. There was a weak but significant positive relationship between age and unbound serum CBZ fraction by simple regression analysis (n = 35, r = 0.368, p = 0.0297). The determined coefficient indicated that only about 14% of variations in unbound serum CBZ fraction can be explained by age, however. In each of Groups 1 and 2, no significant relationship was observed between age and unbound serum CBZ fraction. The effects of age on predictive performance of unbound serum CBZ are relatively small in patients receiving polytherapy. For unbound CBZ-E prediction, each of Methods A and B has no bias to over-or underprediction. The MAE was larger in Method B (MAE = 0.311 μm/L) than Method A (MAE = 0.233 μm/L). The differences in RMSE were small between Methods A (RMSE = 0.349 μm/L) and B (RMSE = 0.333 μm/L), however. Each of Methods A and B may have similar accuracy and precision. © Williams & Wilkins 1996. All Rights Reserved.