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Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment.
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2020-07-11 , DOI: 10.1016/j.pharmthera.2020.107627
Françoise Stanke-Labesque 1 , Elodie Gautier-Veyret 1 , Stephanie Chhun 2 , Romain Guilhaumou 3 ,
Affiliation  

Inflammation is an evolutionary process that allows survival against acute infection or injury. Inflammation is also a pathophysiological condition shared by numerous chronic diseases. In addition, inflammation modulates important drug-metabolizing enzymes and transporters (DMETs), thus contributing to intra- and interindividual variability of drug exposure. A better knowledge of the impact of inflammation on drug metabolism and its related clinical consequences would help to personalize drug treatment.

Here, we summarize the kinetics of inflammatory mediators and the underlying transcriptional and post-transcriptional mechanisms by which they contribute to the inhibition of important DMETs. We also present an updated overview of the effect of inflammation on the pharmacokinetic parameters of most of the drugs that are DMET substrates, for which therapeutic drug monitoring is recommended. Furthermore, we provide opinions on how to integrate the inflammatory status into pharmacogenetics, therapeutic drug monitoring, and population pharmacokinetic strategies to improve the personalization of drug treatment for each patient.



中文翻译:

炎症是药物代谢酶和转运蛋白的主要调节剂:药物治疗个性化的后果。

炎症是一个进化过程,可以抵抗急性感染或损伤。炎症也是许多慢性疾病共有的病理生理状况。此外,炎症调节重要的药物代谢酶和转运蛋白 (DMET),从而导致药物暴露的个体内和个体间变异性。更好地了解炎症对药物代谢的影响及其相关临床后果将有助于个性化药物治疗。

在这里,我们总结了炎症介质的动力学以及它们有助于抑制重要 DMET 的潜在转录和转录后机制。我们还提供了炎症对大多数 DMET 底物药物的药代动力学参数影响的最新概述,建议对其进行治疗药物监测。此外,我们就如何将炎症状态纳入药物遗传学、治疗药物监测和群体药代动力学策略提供意见,以改善每位患者的药物治疗个性化。

更新日期:2020-07-25
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