Verheijen Remy B, Yu Huixin, Schellens Jan H M, Beijnen Jos H, Steeghs Neeltje, Huitema Alwin D R
Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands.
Department of Medical Oncology and Clinical Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands.
Clin Pharmacol Ther. 2017 Nov;102(5):765-776. doi: 10.1002/cpt.787. Epub 2017 Sep 7.
Despite the fact that pharmacokinetic exposure of kinase inhibitors (KIs) is highly variable and clear relationships exist between exposure and treatment outcomes, fixed dosing is still standard practice. This review aims to summarize the available clinical pharmacokinetic and pharmacodynamic data into practical guidelines for individualized dosing of KIs through therapeutic drug monitoring (TDM). Additionally, we provide an overview of prospective TDM trials and discuss the future steps needed for further implementation of TDM of KIs.
尽管激酶抑制剂(KIs)的药代动力学暴露具有高度变异性,且暴露与治疗结果之间存在明确关系,但固定剂量给药仍是标准做法。本综述旨在将现有的临床药代动力学和药效学数据总结为通过治疗药物监测(TDM)对KIs进行个体化给药的实用指南。此外,我们概述了前瞻性TDM试验,并讨论了进一步实施KIs的TDM所需的未来步骤。