Department of Pharmacy, Harborview Medical Center, Seattle, Washington.
School of Pharmacy, University of Washington, Seattle, Washington.
Pharmacotherapy. 2019 Jul;39(7):756-766. doi: 10.1002/phar.2273. Epub 2019 May 30.
Several methods are available to predict unbound (free) phenytoin concentrations in patients with hypoalbuminemia; however, predictive methods have not been evaluated in patients with concurrent hypoalbuminemia and kidney dysfunction or in patients with mild to moderate (estimated glomerular filtration rate [eGFR] 30-90 ml/min/1.73 m ) kidney dysfunction alone. Thus the objective was to evaluate the accuracy and precision of predictive methods to estimate free phenytoin concentrations in patients with varying albumin concentrations and/or kidney dysfunction.
Retrospective chart review.
Large academic medical center.
A total of 344 patients with free and total phenytoin, albumin, and serum creatinine concentrations obtained between November 2012 and May 2017.
Free phenytoin concentrations were estimated in patients without kidney dysfunction using the Winter-Tozer, Anderson, Kane, and Cheng equations. For the analysis in patients with eGFR lower than 90 ml/min/1.73 m , free phenytoin concentrations were estimated using the Shiner-Tozer derivation with adjusted affinity coefficients (C = 0.15, 0.20, 0.25, and 0.30). For both analyses, accuracy of predictive methods was evaluated by P20, the proportion of estimations within 20% of the measured free phenytoin concentration. In 158 patients with normal kidney function/normal albumin concentrations, 73 with normal kidney function/hypoalbuminemia, or 47 with mild kidney dysfunction/normal albumin concentrations, the Anderson method had the highest accuracy (86%, 82%, and 92%, respectively) and highest precision compared with the other methods. In 47 patients with normal albumin concentrations and mild kidney dysfunction or 13 with moderate kidney dysfunction, the free fraction was unchanged, and total phenytoin concentrations accurately reflected free concentrations. In 17 patients with hypoalbuminemia and mild or 17 with moderate kidney dysfunction, the Winter-Tozer (67% and 50%, respectively) and the Anderson (56% and 67%, respectively) methods had the highest accuracy compared with other methods with significantly lower accuracy compared with patients with normal kidney function. In the 14 patients with severe kidney dysfunction and hypoalbuminemia, none of the coefficients had a P20 accuracy greater than 45%.
In patients with normal albumin concentrations, with or without mild or moderate kidney dysfunction and not receiving a protein-binding displacer, the free fraction of phenytoin is unchanged, and it is not necessary to measure a free phenytoin concentration. Free phenytoin concentrations should be measured directly in patients with hypoalbuminemia and kidney dysfunction.
有几种方法可用于预测低白蛋白血症患者的游离（未结合）苯妥英浓度；然而，预测方法尚未在同时存在低白蛋白血症和肾功能不全的患者或仅有轻度至中度（估计肾小球滤过率[eGFR]为 30-90 ml/min/1.73 m ）肾功能不全的患者中进行评估。因此，目的是评估预测方法在白蛋白浓度和/或肾功能不全患者中估算游离苯妥英浓度的准确性和精密度。
回顾性图表审查。
大型学术医疗中心。
共 344 名患者，在 2012 年 11 月至 2017 年 5 月期间获得游离和总苯妥英、白蛋白和血清肌酐浓度。
使用 Winter-Tozer、Anderson、Kane 和 Cheng 方程在无肾功能不全的患者中估算游离苯妥英浓度。对于 eGFR 低于 90 ml/min/1.73 m 的患者的分析，使用 Shiner-Tozer 推导并调整了亲和力系数（C = 0.15、0.20、0.25 和 0.30）来估算游离苯妥英浓度。对于这两种分析，预测方法的准确性通过 P20 进行评估，即估计值与实测游离苯妥英浓度的比例在 20%以内的比例。在 158 名肾功能正常/白蛋白浓度正常的患者、73 名肾功能正常/低白蛋白血症患者或 47 名轻度肾功能不全/白蛋白浓度正常的患者中，与其他方法相比，Anderson 方法具有最高的准确性（分别为 86%、82%和 92%）和最高的精度。在 47 名白蛋白浓度正常和轻度肾功能不全的患者或 13 名中度肾功能不全的患者中，游离分数保持不变，总苯妥英浓度准确反映游离浓度。在 17 名低白蛋白血症和轻度肾功能不全或 17 名中度肾功能不全的患者中，Winter-Tozer（分别为 67%和 50%）和 Anderson（分别为 56%和 67%）方法与其他方法相比具有最高的准确性，与肾功能正常的患者相比准确性明显较低。在 14 名严重肾功能不全和低白蛋白血症的患者中，没有任何系数的 P20 准确性大于 45%。
在白蛋白浓度正常、伴有或不伴有轻度或中度肾功能不全且未接受蛋白结合置换剂的患者中，苯妥英的游离分数保持不变，无需测量游离苯妥英浓度。应直接在低白蛋白血症和肾功能不全的患者中测量游离苯妥英浓度。
