沙库巴曲缬沙坦在维持性血液透析心力衰竭患者中的药代动力学和药效学
Pharmacokinetics and Pharmacodynamics of Sacubitril/Valsartan in Maintenance Hemodialysis Patients with Heart Failure.
作者信息
Feng Zhonglin, Wang Xipei, Zhang Li, Apaer Rizvangul, Xu Lixia, Ma Jianchao, Li Xinyi, Che Huimin, Tang Bin, Xiong Yuwang, Xia Yubin, Xiao Jie, Su Xiaoyan, Wang Yamei, Dou Xianrui, Chen Jinzhong, Mei Lifan, Xue Zhiqiang, Kong Yuanyuan, Li Sijia, Zhang Hong, Lin Ting, Wen Feng, Fu Xia, Tao Yiming, Fu Lei, Li Zhuo, Huang Renwei, Ye Zhiming, He Chaosheng, Shi Wei, Liang Xinling, Ke Guibao, Liu Shuangxin
机构信息
Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Department of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, China.
出版信息
Blood Purif. 2022;51(3):270-279. doi: 10.1159/000519643. Epub 2021 Nov 9.
BACKGROUND
Heart failure (HF) is one of the main comorbidities in patients receiving maintenance hemodialysis (HD). Sacubitril/valsartan (SAC/VAL) is widely used in HF patients with reduced ejection fraction (HFrEF) or HF mid-range ejection fraction (HFmrEF). However, the pharmacokinetic (PK) and pharmacodynamic properties of SAC/VAL in HD patients with HF remain uncertain.
OBJECTIVES
This study aimed to analyze the efficacy and PK properties of SAC/VAL in HD patients with HFrEF or HFmrEF.
METHODS
HD patients with HFrEF or HFmrEF were treated with SAC/VAL 50 or 100 mg twice a day (BID) and the concentrations of valsartan and LBQ657 (active metabolite of SAC) were determined by high-performance liquid chromatography-tandem mass spectrometry during HD and on the days between HD sessions (interval days). N-terminal-pro B-type natriuretic peptide and high-sensitivity troponin T were measured, and left ventricular ejection fraction (LVEF) was evaluated by echocardiography.
RESULTS
The mean maximum plasma concentrations (Cmax) of LBQ657 and VAL on the interval days were 15.46 ± 6.01 and 2.57 ± 1.23 mg/L, respectively. Compared with previous values in patients with severe renal impairment and healthy volunteers, these levels both remained within the safe concentration ranges during treatment with SAC/VAL 100 mg BID. Moreover, SAC/VAL significantly improved LVEF in HD patients with HFrEF or HFmrEF (p < 0.05).
CONCLUSIONS
HD did not remove the SAC metabolite LBQ657 or VAL in patients with HF. However, SAC/VAL 100 mg BID was safe and effective in patients undergoing HD.
背景
心力衰竭（HF）是接受维持性血液透析（HD）患者的主要合并症之一。沙库巴曲缬沙坦（SAC/VAL）广泛用于射血分数降低的心力衰竭（HFrEF）或射血分数中等范围的心力衰竭（HFmrEF）患者。然而，SAC/VAL在HD合并HF患者中的药代动力学（PK）和药效学特性仍不确定。
目的
本研究旨在分析SAC/VAL在HFrEF或HFmrEF的HD患者中的疗效和PK特性。
方法
对HFrEF或HFmrEF的HD患者，每天两次（BID）给予50或100mg SAC/VAL治疗，在HD期间及HD疗程之间的日子（间隔日），通过高效液相色谱-串联质谱法测定缬沙坦和LBQ657（SAC的活性代谢物）的浓度。检测N末端B型利钠肽原和高敏肌钙蛋白T，并通过超声心动图评估左心室射血分数（LVEF）。
结果
间隔日时，LBQ657和VAL的平均最大血浆浓度（Cmax）分别为15.46±6.01和2.57±1.23mg/L。与先前严重肾功能损害患者和健康志愿者的值相比，在每天两次100mg SAC/VAL治疗期间，这些水平均保持在安全浓度范围内。此外，SAC/VAL显著改善了HFrEF或HFmrEF的HD患者的LVEF（p<0.05）。
结论
HD并未清除HF患者体内的SAC代谢物LBQ657或VAL。然而，每天两次100mg的SAC/VAL对接受HD的患者是安全有效的。
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