Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000, Novi Sad, Serbia.
Institute of Pulmonary Diseases, Sremska Kamenica, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Mol Biol Rep. 2020 Jun;47(6):4699-4708. doi: 10.1007/s11033-020-05481-9. Epub 2020 May 15.
Since its discovery in 1945, methotrexate has become a standard therapy for number of diseases, including oncological, inflammatory and pulmonary ones. Major physiological interactions of methotrexate include folate pathway, adenosine, prostaglandins, leukotrienes and cytokines. Methotrexate is used in treatment of pulmonary sarcoidosis as a second line therapy and is drug of choice in patients who are not candidates for corticosteroid therapy, with recommended starting weekly dose of 5-15 mg. Number of studies dealt with methotrexate use in rheumatoid arthritis and oncological patients. Authors are conducting research on oral methotrexate use and pharmacokinetics in chronic sarcoidosis patients and have performed literature research to better understand molecular mechanisms of methotrexate action as well as high level pharmacokinetic considerations. Polyglutamation of methotrexate affects its pharmacokinetic and pharmacodynamic properties and prolongs its effect. Bile excretion plays significant role due to extensive enterohepatic recirculation, although majority of methotrexate is excreted through urine. Better understanding of its pharmacokinetic properties in sarcoidosis patients warrant optimizing therapy when corticosteroids are contraindicated in these patients.
自 1945 年发现以来，甲氨蝶呤已成为多种疾病的标准治疗方法，包括肿瘤、炎症和肺部疾病。甲氨蝶呤的主要生理相互作用包括叶酸途径、腺苷、前列腺素、白三烯和细胞因子。甲氨蝶呤在治疗肺结节病时作为二线治疗药物，在不适合皮质类固醇治疗的患者中是首选药物，推荐的起始剂量为每周 5-15mg。许多研究涉及甲氨蝶呤在类风湿关节炎和肿瘤患者中的应用。作者正在对慢性结节病患者口服甲氨蝶呤的应用和药代动力学进行研究，并进行了文献研究，以更好地了解甲氨蝶呤作用的分子机制以及高水平的药代动力学考虑因素。甲氨蝶呤的多聚谷氨酸化影响其药代动力学和药效学特性，并延长其作用。由于广泛的肠肝循环，胆汁排泄起着重要作用，尽管大部分甲氨蝶呤通过尿液排泄。更好地了解其在结节病患者中的药代动力学特性，需要优化治疗方案，因为在这些患者中皮质类固醇是禁忌的。
