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尼达尼布与口服抗凝剂的相互作用-分子机制与临床意义。

The Interactions of Nintedanib and Oral Anticoagulants-Molecular Mechanisms and Clinical Implications.

机构信息

Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland.

Department of Organic Chemistry, Faculty of Pharmacy, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 2 dr. A. Jurasza St., 85-094 Bydgoszcz, Poland.

出版信息

Int J Mol Sci. 2020 Dec 30;22(1):282. doi: 10.3390/ijms22010282.

DOI:10.3390/ijms22010282
PMID:33396592
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7795697/
Abstract

Nintedanib is a synthetic orally active tyrosine kinase inhibitor, whose main action is to inhibit the receptors of the platelet-derived growth factor, fibroblast growth factor and vascular endothelial growth factor families. The drug also affects other kinases, including Src, Flt-3, LCK, LYN. Nintedanib is used in the treatment of idiopathic pulmonary fibrosis, chronic fibrosing interstitial lung diseases and lung cancer. The mechanism of action suggests that nintedanib should be considered one of the potential agents for inhibiting and revising the fibrosis process related to COVID-19 infections. Due to the known induction of coagulation pathways during COVID-19 infections, possible interaction between nintedanib and anticoagulant seems to be an extremely important issue. In theory, nintedanib could increase the bleeding risk, thrombosis and lead to thrombocytopenia. The data from clinical trials on the concomitant use of nintedanib and antithrombotic agents is very limited as this patient group was within the standard exclusion criteria. Nintedanib is an important therapeutic option, despite its interaction with anticoagulants. If anticoagulant therapy is necessary, the more effective and safer option is the concomitant administration of DOACs and nintedanib, especially when drug-monitored therapy will be used in patients at high risk of bleeding complications.

摘要

尼达尼布是一种合成的、具有口服活性的酪氨酸激酶抑制剂,其主要作用是抑制血小板衍生生长因子、成纤维细胞生长因子和血管内皮生长因子家族的受体。该药物还影响其他激酶,包括Src、Flt-3、LCK、LYN。尼达尼布用于治疗特发性肺纤维化、慢性纤维化间质性肺疾病和肺癌。作用机制表明,尼达尼布应被视为潜在的抑制和修正与 COVID-19 感染相关的纤维化过程的药物之一。由于 COVID-19 感染期间已知会诱导凝血途径,尼达尼布与抗凝剂之间可能存在相互作用,这似乎是一个极其重要的问题。理论上,尼达尼布可能会增加出血风险、血栓形成并导致血小板减少症。由于该患者群体在标准排除标准内,因此关于尼达尼布与抗血栓药物联合使用的临床试验数据非常有限。尽管尼达尼布与抗凝剂存在相互作用,但它仍是一种重要的治疗选择。如果需要抗凝治疗,更有效且更安全的选择是同时给予 DOACs 和尼达尼布,特别是在将药物监测治疗用于有高出血并发症风险的患者时。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/7795697/86115dac0b04/ijms-22-00282-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/7795697/513b2e2004ef/ijms-22-00282-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd5/7795697/fe3458e29998/ijms-22-00282-g001.jpg
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Structural basis of resistance of mutant RET protein-tyrosine kinase to its inhibitors nintedanib and vandetanib.突变 RET 蛋白酪氨酸激酶对其抑制剂尼达尼布和凡德他尼耐药的结构基础。
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J Med Case Rep. 2024 Sep 29;18(1):451. doi: 10.1186/s13256-024-04790-y.
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