Masuda Satohiro, Lemaitre Florian, Barten Markus J, Bergan Stein, Shipkova Maria, van Gelder Teun, Vinks Sander, Wieland Eberhard, Bornemann-Kolatzki Kirsten, Brunet Mercè, de Winter Brenda, Dieterlen Maja-Theresa, Elens Laure, Ito Taihei, Johnson-Davis Kamisha, Kunicki Pawel K, Lawson Roland, Lloberas Nuria, Marquet Pierre, Millan Olga, Mizuno Tomoyuki, Moes Dirk Jan A R, Noceti Ofelia, Oellerich Michael, Pattanaik Smita, Pawinski Tomasz, Seger Christoph, van Schaik Ron, Venkataramanan Raman, Walson Phil, Woillard Jean-Baptiste, Langman Loralie J
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.
Université de Rennes, CHU Rennes, Inserm, EHESP, IRSET-UMR S 1085, Rennes, France.
Ther Drug Monit. 2025 Feb 1;47(1):4-31. doi: 10.1097/FTD.0000000000001250. Epub 2024 Sep 25.
The Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology established the second consensus report to guide therapeutic drug monitoring (TDM) of everolimus (EVR) and its optimal use in clinical practice 7 years after the first version was published in 2016. This version provides information focused on new developments that have arisen in the last 7 years. For the general aspects of the pharmacology and TDM of EVR that have retained their relevance, readers can refer to the 2016 document. This edition includes new evidence from the literature, focusing on the topics updated during the last 7 years, including indirect pharmacological effects of EVR on the mammalian target of rapamycin complex 2 with the major mechanism of direct inhibition of the mammalian target of rapamycin complex 1. In addition, various concepts and technical options to monitor EVR concentrations, improve analytical performance, and increase the number of options available for immunochemical analytical methods have been included. Only limited new pharmacogenetic information regarding EVR has emerged; however, pharmacometrics and model-informed precision dosing have been constructed using physiological parameters as covariates, including pharmacogenetic information. In clinical settings, EVR is combined with a decreased dose of calcineurin inhibitors, such as tacrolimus and cyclosporine, instead of mycophenolic acid. The literature and recommendations for specific organ transplantations, such as that of the kidneys, liver, heart, and lungs, as well as for oncology and pediatrics have been updated. EVR TDM for pancreatic and islet transplantation has been added to this edition. The pharmacodynamic monitoring of EVR in organ transplantation has also been updated. These updates and additions, along with the previous version of this consensus document, will be helpful to clinicians and researchers treating patients receiving EVR.
国际治疗药物监测与临床毒理学协会免疫抑制药物科学委员会在2016年发布第一版共识报告7年后，制定了第二份共识报告，以指导依维莫司（EVR）的治疗药物监测（TDM）及其在临床实践中的最佳应用。此版本提供了聚焦过去7年出现的新进展的信息。对于EVR药理学和TDM中仍具相关性的一般方面，读者可参考2016年的文件。本版纳入了文献中的新证据，重点关注过去7年更新的主题，包括EVR对雷帕霉素靶蛋白复合物2的间接药理作用以及直接抑制雷帕霉素靶蛋白复合物1的主要机制。此外，还包括了监测EVR浓度、提高分析性能以及增加免疫化学分析方法可用选项数量的各种概念和技术选择。关于EVR的新药物遗传学信息出现得较少；然而，已使用包括药物遗传学信息在内的生理参数作为协变量构建了药代动力学和模型指导的精准给药。在临床环境中，EVR与钙调神经磷酸酶抑制剂（如他克莫司和环孢素）剂量的减少联合使用，而非霉酚酸。针对肾脏、肝脏、心脏和肺等特定器官移植以及肿瘤学和儿科的文献及建议已更新。本版新增了胰腺和胰岛移植的EVR TDM。器官移植中EVR的药效学监测也已更新。这些更新和补充内容，连同本共识文件的上一版本，将有助于治疗接受EVR治疗患者的临床医生和研究人员。
