Wang Na, Wu Zhen, Ren Jianwei, Zheng Xin, Han Xiaohong
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
Clin Pharmacokinet. 2024 Dec;63(12):1667-1678. doi: 10.1007/s40262-024-01443-7. Epub 2024 Nov 22.
This study aimed to quantify the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a therapeutic approach for heart failure.
A systematic literature review was conducted to collect pharmacokinetics (PK) and pharmacodynamics (PD) data on empagliflozin, dapagliflozin, and canagliflozin. Population pharmacokinetic models were developed separately for each drug, along with PK/PD turnover models for SGLT2 inhibitors, to describe the time course of NT-proBNP and simulate its changes over 52 weeks.
A total of 42 publications were included in this study. The results showed that baseline NT-proBNP levels, estimated glomerular filtration rate levels, and body weight significantly influenced the therapeutic effects of SGLT2 inhibitors. Among the studied drugs, canagliflozin demonstrated a greater reduction in NT-proBNP at comparable baseline levels.
Baseline NT-proBNP concentration, renal function, and body weight were covariates affecting the efficacy of SGLT2 inhibitors in reducing NT-proBNP. Canagliflozin showed the most favorable treatment outcomes at similar baseline levels. This model-based meta-analysis approach may support further drug development for SGLT2 inhibitors.
本研究旨在量化钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂对N末端B型利钠肽原（NT-proBNP）的影响，作为心力衰竭的一种治疗方法。
进行了一项系统的文献综述，以收集关于恩格列净、达格列净和卡格列净的药代动力学（PK）和药效学（PD）数据。分别为每种药物建立群体药代动力学模型，以及SGLT2抑制剂的PK/PD周转模型，以描述NT-proBNP的时间进程并模拟其在52周内的变化。
本研究共纳入42篇出版物。结果表明，基线NT-proBNP水平、估计肾小球滤过率水平和体重显著影响SGLT2抑制剂的治疗效果。在所研究的药物中，在可比的基线水平下，卡格列净使NT-proBNP降低得更多。
基线NT-proBNP浓度、肾功能和体重是影响SGLT2抑制剂降低NT-proBNP疗效的协变量。在相似的基线水平下，卡格列净显示出最有利的治疗结果。这种基于模型的荟萃分析方法可能支持SGLT2抑制剂的进一步药物开发。
