米多舒林——首个FLT3突变急性髓系白血病的靶向治疗药物

IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY
A. Nowicka, E. Szałek, L. Gil, M. Šíma, A. Karbownik
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引用次数: 0

摘要

急性髓性白血病(AML)患者的预后因遗传因素而异。在大约30%的AML患者中发现fms样酪氨酸激酶3 (FLT3)基因突变。midoblin是第一代多靶点酪氨酸激酶抑制剂,是第一个被批准用于治疗FLT3突变的新诊断AML患者的FLT3抑制剂,与标准诱导和巩固化疗联合使用。然而,正如许多临床试验所显示的那样,这种药物的适应症可能会延长。midoin可以口服,这可以改善患者在治疗期间的舒适度。一般来说,它具有良好的安全性,但与其他药物(如强CYP3A4抑制剂或诱导剂,通常用于AML患者的联合治疗)的相互作用可能导致midoin血浆浓度的变化。因此,这种相互作用可能增加治疗的毒性或降低其治疗效果。本综述的目的是总结目前对米多斯汀的认识,即其作用机制、剂量、不良反应、耐药机制和使用局限性。由于通过细胞色素CYP3A4介导的药物-药物相互作用的管理日益重要,本研究的主要重点是midosvin的药代动力学及其血浆浓度的变异性。作者强调使用midoin进行治疗药物监测是治疗FLT3突变AML患者的一种潜在方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Midostaurin – the First Targeted Therapy Drug for Patients with Acute Myeloid Leukaemia with FLT3 Mutation
The prognosis for patients with acute myeloid leukaemia (AML) varies depending on genetic factors. The presence of mutations in the fms-like tyrosine kinase 3 (FLT3) gene is found in approximately 30% of AML patients. Midostaurin, a first-generation multi-targeted tyrosine kinase inhibitor, is the first FLT3 inhibitor approved for the treatment of newly diagnosed AML patients with the FLT3 mutation in combination with standard induction and consolidation chemotherapy. However, as numerous clinical trials have shown, the list of indications for this drug is likely to be extended. Midostaurin can be administered orally, which improves the patient’s comfort during treatment. In general, it has a favourable safety profile, but interactions with other drugs, such as strong CYP3A4 inhibitors or inducers, which are often used in the concomitant therapy of AML patients, may lead to changes in midostaurin plasma concentrations. In consequence, such interactions may increase the toxicity of the treatment or reduce its therapeutic effect. The aim of this review is to summarise the current knowledge on midostaurin, i.e. its mechanisms of actions, dosage, adverse effects, mechanisms of resistance and limitations to its use. Due to the growing importance of the management of drug-drug interactions mediated via cytochrome CYP3A4, the main focus of this study is the pharmacokinetics of midostaurin and the variability of its plasma concentrations. The Authors emphasise therapeutic drug monitoring with midostaurin as a potential method of managing AML patients with FLT3 mutation.
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来源期刊
CiteScore
0.80
自引率
0.00%
发文量
74
审稿时长
6-12 weeks
期刊介绍: The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General. A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.
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