A. Nowicka, E. Szałek, L. Gil, M. Šíma, A. Karbownik
{"title":"米多舒林——首个FLT3突变急性髓系白血病的靶向治疗药物","authors":"A. Nowicka, E. Szałek, L. Gil, M. Šíma, A. Karbownik","doi":"10.32383/appdr/159470","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4000,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Midostaurin – the First Targeted Therapy Drug for Patients with Acute Myeloid Leukaemia with FLT3 Mutation\",\"authors\":\"A. Nowicka, E. Szałek, L. Gil, M. Šíma, A. Karbownik\",\"doi\":\"10.32383/appdr/159470\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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. 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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.
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.