Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.
Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.
Biomed Pharmacother. 2022 Sep;153:113391. doi: 10.1016/j.biopha.2022.113391. Epub 2022 Jul 12.
Levosimendan was introduced into routine clinical practice in 2000, obtaining approval for the treatment of decompensation of severe chronic heart failure. Levosimendan increases the calcium sensitivity of contractile proteins by binding to myocardial troponin C (cTnC) in a calcium dependent manner. Apart from the mechanism of action of levosimendan, resulting directly in the improvement of heart function, a number of pleiotropic mechanisms have also been identified, including anti-inflammatory, antioxidant and anti-apoptotic effects. Pharmacokinetics of levosimendan is linear in a therapeutic dose range i.e. from 0.05 to 0.2 μg/kg/min. Therapeutic concentration of levosimendan is reached approximately 1 h after the start of intravenous infusion, and steady state is reached within 5 h after continuous infusion initiation. OR-1855 and OR-1896 are the only significant metabolites detected in the systemic circulation after administration of levosimendan. After a 24-hour infusion of levosimendan, the pharmacodynamic effect of the drug is observed for at least one week. Repetitive levosimendan infusions are safe and multiple infusions of levosimendan show a number of benefits. However, experience with multiple doses of levosimendan is scarce. The protocols of clinical trials conducted so far on repeated and intermittent infusions of levosimendan were developed subjectively and were based on the opinion of experts forming a given research team. There is still a need for more clinical research on the multidirectional effect of levosimendan in the group of patients with heart failure. The aim of this review was to summarize most relevant and up-to-date scientific data on pharmacokinetic and pharmacodynamic basis of levosimendan repetitive use in clinical practice that may assist in bedside decision making.
左西孟旦于 2000 年被引入常规临床实践，获批用于治疗严重慢性心力衰竭失代偿。左西孟旦通过与心肌肌钙蛋白 C（cTnC）在钙离子依赖的方式结合，增加收缩蛋白的钙离子敏感性。除了左西孟旦的作用机制，直接导致心功能改善外，还确定了许多多效机制，包括抗炎、抗氧化和抗凋亡作用。左西孟旦的药代动力学在治疗剂量范围内呈线性，即 0.05 至 0.2μg/kg/min。静脉输注开始后约 1 小时达到左西孟旦的治疗浓度，连续输注开始后 5 小时达到稳态。OR-1855 和 OR-1896 是左西孟旦给药后在全身循环中检测到的唯一重要代谢物。静脉输注左西孟旦 24 小时后，观察到药物的药效学作用至少持续一周。重复左西孟旦输注是安全的，多次左西孟旦输注显示出许多益处。然而，多次使用左西孟旦的经验有限。迄今为止，对重复和间歇性输注左西孟旦进行的临床试验方案是主观制定的，基于形成特定研究团队的专家意见。在心力衰竭患者群体中，仍需要更多关于左西孟旦多向作用的临床研究。本综述的目的是总结有关左西孟旦在临床实践中重复使用的药代动力学和药效学基础的最相关和最新的科学数据，这可能有助于床边决策。
