Department of Pharmacy, Hôpital du Sacré-Coeur de Montréal, Montreal, Québec, Canada.
Department of Pharmacy, Complejo Hospitalario de Navarra, Pamplona, Spain.
Pharmacotherapy. 2017 Aug;37(8):900-907. doi: 10.1002/phar.1965. Epub 2017 Jul 18.
Because the pharmacokinetic evaluation of valproic acid (VPA) based on total drug concentration may be misleading in patients with hypoalbuminemia as a result of saturable protein binding and saturable metabolism, we sought to investigate the usefulness of therapeutic drug monitoring of unbound VPA concentration in a real-world clinical context, with a focus on clinically significant neurologic adverse outcomes.
Retrospective analysis.
Large academic tertiary care hospital in Montreal, Canada.
Forty-one adults, hospitalized or followed as outpatients, for whom unbound VPA concentration testing was performed between January 1, 2008, and April 30, 2015. Patients were retrospectively identified by using the hospital's central laboratory database.
In the multiple linear regression analysis, the two variables that significantly predicted unbound VPA concentration were total VPA concentration (p<0.001) and albumin concentration (p<0.001). The correlation between total VPA concentration and the number of neurologic adverse symptoms was 0.187 (p=0.241), whereas the correlation between unbound VPA concentration and the number of neurologic adverse symptoms was 0.384 (p=0.013). The performance of total and unbound VPA concentrations in predicting the presence of at least one neurologic adverse symptom, as determined by the receiver operating characteristic curve, was 0.642 (95% confidence interval [CI] 0.449-0.836, p=0.167) and 0.776 (95% CI 0.629-0.923, p=0.007), respectively.
This study showed that in the presence of hypoalbuminemia, high unbound VPA concentrations can be observed despite normal or low total VPA concentrations. It also demonstrated that high unbound VPA concentrations are associated with clinically significant neurologic adverse symptoms. Clinicians should be aware that unbound VPA concentration monitoring may be required in the presence of hypoalbuminemia.
由于结合蛋白饱和度和代谢饱和度的影响，对于低蛋白血症患者，基于总药物浓度的丙戊酸（VPA）药代动力学评估可能会产生误导，因此我们旨在研究在实际临床环境中，监测游离 VPA 浓度在治疗药物监测中的作用，重点关注有临床意义的神经不良结局。
回顾性分析。
加拿大蒙特利尔的一家大型学术型三级保健医院。
41 名成年人，住院或作为门诊患者接受治疗，他们在 2008 年 1 月 1 日至 2015 年 4 月 30 日期间进行了游离 VPA 浓度检测。通过医院的中心实验室数据库对患者进行回顾性鉴定。
在多元线性回归分析中，两个显著预测游离 VPA 浓度的变量是总 VPA 浓度（p<0.001）和白蛋白浓度（p<0.001）。总 VPA 浓度与神经不良症状数量之间的相关性为 0.187（p=0.241），而游离 VPA 浓度与神经不良症状数量之间的相关性为 0.384（p=0.013）。通过受试者工作特征曲线确定的总 VPA 浓度和游离 VPA 浓度在预测至少一种神经不良症状的存在方面的表现分别为 0.642（95%置信区间[CI]0.449-0.836，p=0.167）和 0.776（95% CI 0.629-0.923，p=0.007）。
本研究表明，在存在低蛋白血症的情况下，尽管总 VPA 浓度正常或较低，仍可观察到高游离 VPA 浓度。还表明，高游离 VPA 浓度与有临床意义的神经不良症状相关。临床医生应该意识到，在存在低蛋白血症的情况下，可能需要进行游离 VPA 浓度监测。
