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基于液相色谱-质谱联用的治疗药物监测在精准医学中的实用性、前景及局限性。

Utility, promise, and limitations of liquid chromatography-mass spectrometry-based therapeutic drug monitoring in precision medicine.

机构信息

Segal Cancer Proteomics Centre, McGill University, Montreal, Quebec, Canada.

Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.

出版信息

J Mass Spectrom. 2021 Nov;56(11):e4788. doi: 10.1002/jms.4788. Epub 2021 Nov 4.

Abstract

Therapeutic drug monitoring (TDM) is typically referred to as the measurement of the concentration of drugs in patient blood. Although in the past, TDM was restricted to drugs with a narrow therapeutic range in order to avoid drug toxicity, TDM has recently become a major tool for precision medicine being applied to many more drugs. Through compensating for interindividual differences in a drug's pharmacokinetics, improved dosing of individual patients based on TDM ensures maximum drug effectiveness while minimizing side effects. This is especially relevant for individuals that present a particularly high intervariability in pharmacokinetics, such as newborns, or for critically/severely ill patients. In this article, we will review the applications for and limitations of TDM, discuss for which patients TDM is most beneficial and why, examine which techniques are being used for TDM, and demonstrate how mass spectrometry is increasingly becoming a reliable and convenient alternative for the TDM of different classes of drugs. We will also highlight the advances, challenges, and limitations of the existing repertoire of TDM methods and discuss future opportunities for TDM-based precision medicine.

摘要

治疗药物监测(therapeutic drug monitoring,TDM)通常是指测量患者血液中药物浓度。虽然过去 TDM 仅限于治疗窗较窄的药物,以避免药物毒性,但最近 TDM 已成为精准医学的主要工具,应用于更多的药物。通过补偿药物药代动力学的个体差异,基于 TDM 的个体化患者剂量调整确保了最大的药物疗效,同时最小化副作用。这对于那些在药代动力学方面表现出特别高的变异性的个体,如新生儿,或对于危重病患者来说尤其重要。在本文中,我们将回顾 TDM 的应用和局限性,讨论哪些患者最受益于 TDM 以及原因,检查用于 TDM 的技术,展示质谱技术如何越来越成为不同类别药物 TDM 的可靠和方便的替代方法。我们还将强调现有 TDM 方法的进展、挑战和局限性,并讨论基于 TDM 的精准医学的未来机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e32/8597589/42a1c4247330/JMS-56-e4788-g001.jpg

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