Yukawa E, Higuchi S, Aoyama T
Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Pharmacobiodyn. 1988 Nov;11(11):736-43. doi: 10.1248/bpb1978.11.736.
Phenytoin (PHT) dosage adjustment in a clinical situation is difficult because of the nonlinear metabolism of the drug. Therefore, many techniques have been advocated to aid in dosage adjustments based on single-point PHT concentration determined at steady-state (SS). We retrospectively investigated seven methods in a population of 90 outpatients treated with PHT. The dose needed to achieve a desired PHT concentration at SS was calculated based on an observed SS dose-concentration pair using the Richens and Dunlop nomogram (RD), the Rambeck nomogram, the Martin nomogram, the Chiba nomogram, a population clearance method, the Wagner dosing equation and the Bayesian feedback method(B). Mean prediction error, mean absolute error (MAE), and root mean squared error (RMSE) were separately calculated for each method, and served as a measure of prediction bias and precision. The MAE and RMSE were lowest for method B (MAE = 28.7 mg/d, RMSE = 36.8 mg/d), followed by method RD (MAE = 30.3 mg/d, RMSE = 40.8 mg/d). Therefore, we recommend the use of method B to make routine PHT dosage adjustments in pediatric patients when only one dose and one concentration are available.
由于苯妥英（PHT）的非线性代谢，在临床情况下调整其剂量很困难。因此，人们提倡了许多技术来辅助基于稳态（SS）时测定的单点PHT浓度进行剂量调整。我们回顾性研究了90例接受PHT治疗的门诊患者群体中的七种方法。使用里琴斯和邓洛普诺模图（RD）、拉姆贝克诺模图、马丁诺模图、千叶诺模图、群体清除率法、瓦格纳给药方程和贝叶斯反馈法（B），根据观察到的SS剂量-浓度对计算在SS时达到所需PHT浓度所需的剂量。分别计算每种方法的平均预测误差、平均绝对误差（MAE）和均方根误差（RMSE），并将其作为预测偏差和精度的度量。方法B的MAE和RMSE最低（MAE = 28.7 mg/d，RMSE = 36.8 mg/d），其次是方法RD（MAE = 30.3 mg/d，RMSE = 40.8 mg/d）。因此，我们建议在仅有一个剂量和一个浓度可用时，使用方法B对儿科患者进行常规PHT剂量调整。
