Kodama Y, Kuranari M, Kodama H, Tsutsumi K, Fujii I, Takeyama M
Department of Clinical Pharmacy, Oita Medical University, Japan.
J Clin Pharmacol. 1995 Oct;35(10):995-1002. doi: 10.1002/j.1552-4604.1995.tb04016.x.
In a previous study, an equation with in vivo population binding parameters of carbamazepine and carbamazepine-10, 11-epoxide (CBZ-E) to serum proteins for the relation between unbound and bound serum concentrations was defined. A review by Pynnönen indicates that the average bound/unbound plasma fraction ratio is 3.0 for carbamazepine and 1.0 for CBZ-E. In this study, the ability of equations with in vivo population binding parameters of the previous study (method 1) or with the average bound/unbound plasma fraction ratio of 3.0 of Pynnönen (method 2) to predict the bound serum carbamazepine concentration was retrospectively evaluated using 85 serum samples from 46 patients with epilepsy taking carbamazepine polytherapy. In 21 serum samples from 16 patients, the ability of these equations to predict bound serum CBZ-E concentration was also determined with in vivo population binding parameters from the previous study (method A) or with the average bound/unbound plasma fraction ratio of 1.0 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 showed a bias to overpredict bound serum carbamazepine. The MAE and RMSE were significantly smaller with method 2 (MAE = 2.4 mumol/L; RMSE = 3.2 mumol/L) than with method 1 (MAE = 4.1 mumol/L; RMSE = 4.8 mumol/L). Method 2 was superior to method 1 in terms of accuracy and precision. For bound CBZ-E prediction, method B had a bias to underprediction. The MAE and RMSE were smaller with method A (MAE = 0.581 mumol/L; RMSE = 0.796 mumol/L) than with method B (MAE = 0.724 mumol/L; RMSE = 0.905 mumol/L). Method A was superior to method B in terms of accuracy and precision.
在之前的一项研究中，定义了一个包含卡马西平及卡马西平 - 10,11 - 环氧化物（CBZ - E）与血清蛋白的体内群体结合参数的方程，用于描述游离和结合血清浓度之间的关系。Pynnönen的一项综述表明，卡马西平的平均结合/游离血浆分数比为3.0，CBZ - E为1.0。在本研究中，使用来自46例接受卡马西平联合治疗的癫痫患者的85份血清样本，回顾性评估了采用先前研究的体内群体结合参数的方程（方法1）或采用Pynnönen的平均结合/游离血浆分数比3.0的方程（方法2）预测结合血清卡马西平浓度的能力。在来自16例患者的21份血清样本中，还采用先前研究的体内群体结合参数（方法A）或Pynnönen的平均结合/游离血浆分数比1.0（方法B）确定了这些方程预测结合血清CBZ - E浓度的能力。计算了每种方法的平均预测误差、平均绝对预测误差（MAE）和均方根误差（RMSE），这些值作为预测偏差和精度的度量。方法1显示出高估结合血清卡马西平的偏差。方法2的MAE和RMSE（MAE = 2.4 μmol/L；RMSE = 3.2 μmol/L）显著小于方法1（MAE = 4.1 μmol/L；RMSE = 4.8 μmol/L）。方法2在准确性和精度方面优于方法1。对于结合CBZ - E的预测，方法B有低估的偏差。方法A的MAE和RMSE（MAE = 0.581 μmol/L；RMSE = 0.796 μmol/L）小于方法B（MAE = 0.724 μmol/L；RMSE = 0.905 μmol/L）。方法A在准确性和精度方面优于方法B。
