Determinants of free serum valproate concentration: A prospective study in patients on divalproex sodium monotherapy
Determinants of free serum valproate concentration: A prospective study in patients on divalproex sodium monotherapy
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DOI：
10.1016/j.seizure.2018.04.012
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发表时间：
2018-07-01
影响因子：
3
通讯作者：
Beydoun, Ahmad
中科院分区：
文献类型：
--
作者：
Nasreddine, Wassim;Dirani, Maya;Beydoun, Ahmad
目的：评估影响丙戊酸 (WA) 游离分数的变量，并建立根据总 VPA 浓度计算游离 VPA 浓度的方程。方法：从参加前瞻性 VPA 单药治疗试验的患者收集总和游离 VPA 浓度谷值。包括所有可用的谷总 VPA 浓度和游离 VPA 浓度配对数据。在多变量模型中评估单变量分析的显着变量。结果：总共可获得 902 个伴随的总 VPA 浓度和游离 VPA 浓度。多变量分析表明，VPA 总浓度、年龄和性别与不含 VPA 的比例显着相关。然而，VPA 总浓度的效应大小明显高于性别和年龄的效应大小。对于 20 至 60 μg/mL 之间的总 VPA 浓度，不含 VPA 的部分保持稳定在 10% 左右，随后随着浓度的升高而线性增加。总 VPA 浓度和游离 VPA 浓度相关的散点图显示，二次方程最适合数据，占游离 VPA 浓度方差的 88%。结论：总 VPA 浓度的增加分别导致 VPA 游离分数和游离 WA 浓度相应的线性和非线性上升。当 VPA 总浓度达到 60 μg/mL 时，VPA 的每日总剂量应以较小的增量增加。当需要药物监测时，我们建议测量游离 VPA 浓度。如果此测试不可用，并且对于白蛋白水平正常的患者，可以使用生成的方程从总 VPA 浓度进行预测。 (C) 2018 年英国癫痫协会。由爱思唯尔有限公司出版。保留所有权利。
Purpose: To evaluate variables affecting the valproate (WA) free fraction and develop an equation for computing free VPA concentration from total VPA concentration.Methods: Trough total and free VPA concentrations were collected from patients who participated in a prospective VPA monotherapy trial. All available paired data of trough total and free VPA concentrations were included. Significant variables from the univariate analysis were evaluated in a multivariate model.Results: A total of 902 concomitant total and free VPA concentrations were available. Multivariate analysis showed that total VPA concentration, age and gender were significantly associated with VPA free fraction. However, the effect size of total VPA concentration was substantially higher than that of gender and age. VPA free fraction remained stable at around 10% for total VPA concentration between 20 and 60 mu g/mL with subsequent linear increases for higher concentration. A scatter plot correlating total and free VPA concentrations showed that a quadratic equation best fitted the data, accounting for 88% of the free VPA concentration variance.Conclusions: An increase in the total VPA concentration results in corresponding linear and non-linear rise in the VPA free fraction and free WA concentration, respectively. The total daily dose of VPA should be increased in smaller increments whenever a total VPA concentration of 60 mu g/mL is reached. When drug monitoring is needed, we recommend measuring the free VPA concentration. If this test is unavailable, and for patients with normal albumin levels, it can be predicted from the total VPA concentration using the generated equation. (C) 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.