Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
BMC Med Inform Decis Mak. 2012 Feb 14;12:7. doi: 10.1186/1472-6947-12-7.
Therapeutic drug monitoring of phenytoin by measurement of plasma concentrations is often employed to optimize clinical efficacy while avoiding adverse effects. This is most commonly accomplished by measurement of total phenytoin plasma concentrations. However, total phenytoin levels can be misleading in patients with factors such as low plasma albumin that alter the free (unbound) concentrations of phenytoin. Direct measurement of free phenytoin concentrations in plasma is more costly and time-consuming than determination of total phenytoin concentrations. An alternative to direct measurement of free phenytoin concentrations is use of the Sheiner-Tozer equation to calculate an adjusted phenytoin that corrects for the plasma albumin concentration. Innovative medical informatics tools to identify patients who would benefit from adjusted phenytoin calculations or from laboratory measurement of free phenytoin are needed to improve safety and efficacy of phenytoin pharmacotherapy. The electronic medical record for an academic medical center was searched for the time period from August 1, 1996 to November 30, 2010 for patients who had total phenytoin and free phenytoin determined on the same blood draw, and also a plasma albumin measurement within 7 days of the phenytoin measurements. The measured free phenytoin plasma concentration was used as the gold standard.
In this study, the standard Sheiner-Tozer formula for calculating an estimated (adjusted) phenytoin level more frequently underestimates than overestimates the measured free phenytoin relative to the respective therapeutic ranges. Adjusted phenytoin concentrations provided superior classification of patients than total phenytoin measurements, particularly at low albumin concentrations. Albumin plasma concentrations up to 7 days prior to total phenytoin measurements can be used for adjusted phenytoin concentrations.
The results suggest that a measured free phenytoin should be obtained where possible to guide phenytoin dosing. If this is not feasible, then an adjusted phenytoin can supplement a total phenytoin concentration, particularly for patients with low plasma albumin.
通过测量血浆浓度来监测苯妥英的治疗药物，通常用于优化临床疗效，同时避免不良反应。这通常是通过测量总苯妥英血浆浓度来实现的。然而，在存在改变苯妥英游离（未结合）浓度的因素（如低血浆白蛋白）的患者中，总苯妥因水平可能会产生误导。与测定总苯妥英浓度相比，直接测定血浆中游离苯妥英浓度更昂贵且耗时。替代直接测量游离苯妥英浓度的方法是使用 Sheiner-Tozer 方程来计算校正的苯妥英，以校正血浆白蛋白浓度。需要创新的医疗信息工具来识别从校正的苯妥英计算或从实验室测量游离苯妥英中受益的患者，以提高苯妥英治疗的安全性和疗效。在学术医疗中心的电子病历中，搜索了 1996 年 8 月 1 日至 2010 年 11 月 30 日期间的患者，这些患者在同一血液采集时测定了总苯妥英和游离苯妥英，并且在苯妥英测定的 7 天内还测定了血浆白蛋白。使用测量的游离苯妥英血浆浓度作为金标准。
在本研究中，用于计算估计（校正）苯妥英水平的标准 Sheiner-Tozer 公式与相应的治疗范围相比，更频繁地低估而不是高估测量的游离苯妥英。与总苯妥英测量相比，校正后的苯妥英浓度可更好地对患者进行分类，特别是在白蛋白浓度较低时。总苯妥英测量前 7 天内的白蛋白血浆浓度可用于校正后的苯妥英浓度。
结果表明，应尽可能获得测量的游离苯妥英以指导苯妥英的剂量。如果这不可行，则可以补充总苯妥英浓度的校正后的苯妥英，尤其是对于低血浆白蛋白的患者。
