基于血清白蛋白的丙戊酸浓度校正的准确性。
Accuracy of Valproic Acid Concentration Correction Based on Serum Albumin.
机构信息
Medical University of South Carolina Health, Charleston, SC, USA.
出版信息
Neurocrit Care. 2019 Apr;30(2):301-306. doi: 10.1007/s12028-018-0627-4.
BACKGROUND
Patient-specific factors can alter the pharmacokinetic disposition of valproic acid. Specifically, the free fraction of valproic acid can increase substantially in patients with hypoalbuminemia or as serum drug concentrations rise due to saturable protein binding. Direct measurement of free serum drug concentrations allows for accurate assessment of drug levels, but the assay may not be readily available in all institutions. The effect of hypoalbuminemia on free fraction has been quantified and serves as the basis of an equation used to "correct" measured total valproic acid concentrations. The aim of this study was to evaluate the accuracy of the equation.
METHODS
This retrospective study included adult patients with measurable free and total valproic acid concentrations between July 2014 and June 2017. The primary aim was to assess the relationship between measured and predicted free valproic acid concentrations. Free levels were categorized as subtherapeutic, therapeutic, or supratherapeutic based on the reference range of 7-23 mg/L. Concordance was defined as measured and predicted concentrations falling within the same category.
RESULTS
The analysis included 174 patients with a median age of 58 years and a median albumin of 3 g/dL. The majority of patients were hospitalized (88.5%). Concordance occurred in 56.9% of samples. A Spearman's correlation coefficient of 0.60 (p < 0.001) was found between the measured and predicted free valproic acid concentrations. Concordance of concentrations was 42% for ICU patients, 63% for floor patients, and 65% for outpatients. Of those with discordant concentrations, 97% of the predicted concentrations underestimated the measured concentrations.
CONCLUSIONS
There is discordance between predicted and measured free serum valproic acid concentrations when using the proposed equation. Because of the potential impact of underestimation and variability of free valproic acid concentrations, a measured free level is the ideal option for therapeutic drug monitoring of valproic acid.
背景
个体患者因素可能改变丙戊酸的药代动力学分布。具体来说，由于蛋白结合饱和，低白蛋白血症或血清药物浓度升高可使丙戊酸的游离分数大幅增加。直接测量游离血清药物浓度可准确评估药物水平，但并非所有机构都能轻易获得该检测。已经对低白蛋白血症对游离分数的影响进行了量化，并以此为基础建立了一个方程，用于“校正”测量的总丙戊酸浓度。本研究旨在评估该方程的准确性。
方法
本回顾性研究纳入了 2014 年 7 月至 2017 年 6 月间可测量游离和总丙戊酸浓度的成年患者。主要目的是评估测量和预测游离丙戊酸浓度之间的关系。根据 7-23mg/L 的参考范围，将游离水平分为治疗范围以下、治疗范围和治疗范围以上。符合率定义为测量和预测浓度属于同一类别。
结果
该分析纳入了 174 名中位年龄为 58 岁且中位白蛋白水平为 3g/dL 的患者。大多数患者住院（88.5%）。符合率为 56.9%。测量和预测游离丙戊酸浓度之间存在 0.60 的斯皮尔曼相关系数（p<0.001）。ICU 患者的符合率为 42%，普通病房患者为 63%，门诊患者为 65%。浓度不一致的患者中，97%的预测浓度低估了测量浓度。
结论
使用所提出的方程时，预测和测量的游离血清丙戊酸浓度之间存在差异。由于游离丙戊酸浓度低估和变异性的潜在影响，测量的游离水平是丙戊酸治疗药物监测的理想选择。
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