Can serum albumin level affect the pharmacological action of tolvaptan in patients with liver cirrhosis? A post hoc analysis of previous clinical trials in Japan.
Can serum albumin level affect the pharmacological action of tolvaptan in patients with liver cirrhosis? A post hoc analysis of previous clinical trials in Japan.
复制标题
DOI：
10.1007/s00535-015-1052-5
复制
发表时间：
2015-10
影响因子：
6.3
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Sakaida I;Nakajima K;Okita K;Hori M;Izumi T;Sakurai M;Shibasaki Y;Tachikawa S;Tsubouchi H;Oka H;Kobayashi H
低白蛋白血症患者对增加袢利尿剂剂量常常无效。因此，我们进行了事后分析，以研究托伐普坦的药理作用及其是否依赖于血清白蛋白水平。这项分析是基于之前在对传统利尿剂反应不足的肝硬化患者中进行的四项托伐普坦临床试验。我们分析了初始24小时累积尿量较基线的变化与基线血清白蛋白水平之间的相关性，并评估了托伐普坦反应的潜在预测因素。肝硬化患者安慰剂组的相关系数为0.029，7.5 mg托伐普坦组的相关系数为-0.112。无论血清白蛋白水平如何，托伐普坦给药均引起稳定反应。托伐普坦的使用被确定为药理作用的重要预测因子，并显示在肝硬化患者中初始尿量改变885 mL（P < 0.0001）。在该事后分析中，无论血清白蛋白水平如何，托伐普坦均使初始尿量较基线增加。在袢利尿剂反应不足的患者中，使用托伐普坦作为袢利尿剂的辅助治疗可视为最佳治疗选择。
Patients with hypoalbuminemia often fail to respond to increased doses of loop diuretics. We therefore performed a post hoc analysis to investigate the pharmacological action of tolvaptan and whether it is dependent on the serum albumin level. This analysis was based on four previous clinical trials of tolvaptan in patients with liver cirrhosis who exhibited insufficient response to conventional diuretics. We analyzed the correlation between the change in the initial 24-h cumulative urine volume from baseline and the serum albumin level at baseline, and assessed potential predictive factors of response to tolvaptan. The correlation coefficient was 0.029 in the placebo group and −0.112 in the 7.5 mg tolvaptan group of patients with liver cirrhosis. Administration of tolvaptan provoked a stable response regardless of the serum albumin level. Tolvaptan use was identified as a significant predictor of pharmacological action, and was shown to change the initial urine volume by 885 mL (P < 0.0001) in liver cirrhosis patients. In this post hoc analysis, tolvaptan increased the initial urine volume from baseline regardless of serum albumin levels. Use of tolvaptan as an add-on therapy to loop diuretics can be considered an optimal therapeutic option in patients with insufficient response to loop diuretics.