Yuen G J, Latimer P T, Littlefield L C, Mackey R W
School of Pharmacy, University of Maryland, Baltimore.
Clin Pharmacokinet. 1989 Apr;16(4):254-60. doi: 10.2165/00003088-198916040-00004.
Phenytoin dosing in paediatric patients is complicated both by alterations in patient requirements due to growth and maturation changes and by the capacity-limited characteristics of phenytoin metabolism. This study examines 2 pharmacokinetic methods to adjust phenytoin dosage based on a single dosing-rate/steady-state serum phenytoin concentration pair. A Bayesian forecaster and a fixed parameter [rate of metabolism (Vmax)] method were examined with previously published sets of a priori parameter estimates. The fixed Vmax method was utilised with the parameter derived from native Japanese (method 1), US Caucasian (method 2) and European (method 3) patients. The Bayesian forecaster used a priori parameter estimates obtained from native Japanese (method 4) and European (method 5) patients. Each method was examined retrospectively in 34 paediatric patients with a total of 48 predictions possible. Measures of absolute predictability, bias (mean error, % dose) and precision (root mean squared error, % dose), were -3.58/12.2, -1.51/12.2, 4.06/9.96, -4.38/13.2, and -3.10/11.5, for methods 1, 2, 3, 4 and 5, respectively. There was no significant difference among the 5 methods. However, the Bayesian algorithm tended to be more robust over a broad range of situations, providing predictions in all cases. The fixed Vmax methods could not provide predictions in every case. Finally, all methods had a significant number of overpredictions of dosage. Poorer results were observed when prediction of steady-state serum concentrations were performed, partly due to the retrospective nature of the study. We conclude that close monitoring of patients, regardless of the method chosen to adjust dosage, is recommended.
小儿患者的苯妥英钠剂量确定较为复杂，这是由于生长和成熟变化导致患者需求改变，以及苯妥英钠代谢的容量限制特性所致。本研究考察了两种基于单一给药速率/稳态血清苯妥英钠浓度对来调整苯妥英钠剂量的药代动力学方法。使用先前发表的先验参数估计集，对贝叶斯预测器和固定参数[代谢速率（Vmax）]方法进行了考察。固定Vmax方法采用了源自日本本土患者（方法1）、美国白种人患者（方法2）和欧洲患者（方法3）的参数。贝叶斯预测器使用了从日本本土患者（方法4）和欧洲患者（方法5）获得的先验参数估计值。对34例儿科患者进行了回顾性研究，总共可能进行48次预测。方法1、2、3、4和5的绝对可预测性、偏差（平均误差，%剂量）和精密度（均方根误差，%剂量）的测量值分别为-3.58/12.2、-1.51/12.2、4.06/9.96、-4.38/13.2和-3.10/11.5。这5种方法之间无显著差异。然而，贝叶斯算法在广泛的情况下往往更稳健，在所有情况下均能提供预测。固定Vmax方法并非在每种情况下都能提供预测。最后，所有方法都有大量剂量预测过高的情况。在进行稳态血清浓度预测时观察到较差的结果，部分原因是研究的回顾性性质。我们得出结论，无论选择何种方法调整剂量，都建议对患者进行密切监测。
