Suppr超能文献

预测非酒精性脂肪性肝炎患者药物药代动力学的改变及药物不良反应风险

Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.

作者信息

Marie Solène, Frost Kayla L, Hau Raymond K, Martinez-Guerrero Lucy, Izu Jailyn M, Myers Cassandra M, Wright Stephen H, Cherrington Nathan J

机构信息

College of Pharmacy, Department of Pharmacology & Toxicology, University of Arizona, Tucson, AZ 85721, USA.

College of Medicine, Department of Physiology, University of Arizona, Tucson, AZ 85724, USA.

出版信息

Acta Pharm Sin B. 2023 Jan;13(1):1-28. doi: 10.1016/j.apsb.2022.08.018. Epub 2022 Aug 28.

Abstract

The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and transporters. Non-alcoholic steatohepatitis (NASH) causes disease-specific alterations to the absorption, distribution, metabolism, and excretion (ADME) processes, including a decrease in protein expression of basolateral uptake transporters, an increase in efflux transporters, and modifications to enzyme activity. This can result in increased drug exposure and adverse drug reactions (ADRs). Our goal was to predict drugs that pose increased risks for ADRs in NASH patients. Bibliographic research identified 71 drugs with reported ADRs in patients with liver disease, mainly non-alcoholic fatty liver disease (NAFLD), 54 of which are known substrates of transporters and/or metabolizing enzymes. Since NASH is the progressive form of NAFLD but is most frequently undiagnosed, we identified other drugs at risk based on NASH-specific alterations to ADME processes. Here, we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH, based on their transport and/or metabolism processes. It encompasses drugs from various pharmacological classes for which ADRs may occur when used in NASH patients, especially when eliminated through multiple pathways altered by the disease. Therefore, these results may inform clinicians regarding the selection of drugs for use in NASH patients.

摘要

肝脏通过药物代谢酶和转运体在药物的药代动力学中发挥核心作用。非酒精性脂肪性肝炎(NASH)会导致吸收、分布、代谢和排泄(ADME)过程出现疾病特异性改变,包括基底外侧摄取转运体的蛋白质表达降低、外排转运体增加以及酶活性改变。这可能导致药物暴露增加和药物不良反应(ADR)。我们的目标是预测在NASH患者中导致ADR风险增加的药物。文献研究确定了71种在肝病患者(主要是非酒精性脂肪性肝病(NAFLD))中有ADR报告的药物,其中54种是已知的转运体和/或代谢酶底物。由于NASH是NAFLD的进展形式,但最常未被诊断出来,我们根据ADME过程中NASH特异性改变确定了其他有风险的药物。在此,我们基于其转运和/或代谢过程,列出了另一组71种在NASH中有药代动力学破坏风险的药物。它涵盖了各种药理学类别的药物,这些药物在NASH患者中使用时可能会出现ADR,特别是当通过该疾病改变的多种途径消除时。因此,这些结果可能会为临床医生在为NASH患者选择用药时提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d28/9939324/8d428ab37fa9/ga1.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验