Evans Kayleigh, Seifert Roland
Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 , Hannover, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 18. doi: 10.1007/s00210-025-04443-x.
As Na-K-ATPase (NKA) inhibitors ('cardiac glycosides') have declining rates of prescriptions because of their narrow therapeutic window, high toxicity and questionable clinical efficacy in cardiological indications, the question arises what the future of these drugs entails. In this paper, we researched and analysed newer uses of these drugs outside of their traditional indications, also referred to as repurposing. On ClinicalTrials.gov, we analysed the trials on NKA inhibitors including the scientific value of published trials. Of 306 trials to be analysed, only 40 were for repurposed use, of which 17 had a publication. Malignant diseases and foetal demise for late abortion are the most prominent indications. However, the quality of the clinical studies analysed was far from satisfying. Not a single study provided compelling evidence for a new clinical indication of NKA inhibitors at clinically relevant drug doses. NKA inhibitors could still have a future, specifically as part of oncological treatments. Different molecular mechanisms of action beyond NKA inhibition may be relevant for this use. However, further research is still required to see if in vitro effects can be translated to in vivo as well, which is the major bottleneck in repurposing NKA inhibitors in their narrow therapeutic window and high toxicity, unless specifically exploited in foetal demise.
由于钠钾-ATP酶（NKA）抑制剂（“强心苷”）的治疗窗狭窄、毒性高且在心脏病适应症中的临床疗效存疑，其处方率不断下降，这些药物的未来走向成为问题。在本文中，我们研究并分析了这些药物在传统适应症之外的新用途，即药物再利用。在ClinicalTrials.gov上，我们分析了关于NKA抑制剂的试验，包括已发表试验的科学价值。在要分析的306项试验中，只有40项是用于药物再利用的，其中17项有出版物。恶性疾病和晚期流产导致的胎儿死亡是最突出的适应症。然而，所分析的临床研究质量远不能令人满意。没有一项研究能提供令人信服的证据，证明在临床相关药物剂量下NKA抑制剂有新的临床适应症。NKA抑制剂仍可能有未来，特别是作为肿瘤治疗的一部分。除了抑制NKA之外的不同分子作用机制可能与这种用途相关。然而，仍需要进一步研究，以确定体外效应是否也能转化为体内效应，这是在其狭窄治疗窗和高毒性情况下将NKA抑制剂用于药物再利用的主要瓶颈，除非在胎儿死亡方面有特殊应用。
