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非酒精性脂肪性肝病中药物转运和代谢的变化及其临床意义。

Changes in drug transport and metabolism and their clinical implications in non-alcoholic fatty liver disease.

机构信息

a Bethlehem Center of Health , Department of Medicine , Stolberg/Rhineland , Germany.

b Division of Hepatology, Department of Medicine II , University of Würzburg , Würzburg , Germany.

出版信息

Expert Opin Drug Metab Toxicol. 2017 Jun;13(6):625-640. doi: 10.1080/17425255.2017.1314461. Epub 2017 Apr 11.

Abstract

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising, especially in Western countries. Drug treatment in patients with NAFLD is common since it is linked to other conditions like diabetes, obesity, and cardiovascular disease. Consequently, changes in drug metabolism may have serious clinical implications. Areas covered: A literature search for studies in animal models or patients with obesity, fatty liver, non-alcoholic steatohepatitis (NASH) or NASH cirrhosis published before November 2016 was performed. After discussing epidemiology and animal models for NAFLD, we summarized both basic as well as clinical studies investigating changes in drug transport and metabolism in NAFLD. Important drug groups were assessed separately with emphasis on clinical implications for drug treatment in patients with NAFLD. Expert opinion: Given the frequency of NAFLD even today, a high degree of drug treatment in NAFLD patients appears safe and well-tolerated despite considerable changes in hepatic uptake, distribution, metabolism and transport of drugs in these patients. NASH causes changes in biliary excretion, systemic concentrations, and renal handling of drugs leading to alterations in drug efficacy or toxicity under specific circumstances. Future clinical drug studies should focus on this special patient population in order to avoid serious adverse events in NAFLD patients.

摘要

非酒精性脂肪性肝病(NAFLD)的发病率正在上升,尤其是在西方国家。由于 NAFLD 与糖尿病、肥胖和心血管疾病等其他疾病有关,因此患者经常接受药物治疗。因此,药物代谢的变化可能具有严重的临床意义。

涵盖领域

对 2016 年 11 月之前发表的关于肥胖、脂肪肝、非酒精性脂肪性肝炎(NASH)或 NASH 肝硬化的动物模型或患者研究进行了文献检索。在讨论了 NAFLD 的流行病学和动物模型之后,我们总结了研究 NAFLD 中药物转运和代谢变化的基础和临床研究。分别评估了重要的药物类别,并重点讨论了这些患者药物治疗的临床意义。

专家意见

鉴于今天 NAFLD 的发病率,即使在这些患者中,药物治疗的频率也很高,尽管这些患者的肝脏摄取、分布、代谢和转运药物发生了相当大的变化,但药物治疗似乎是安全且耐受良好的。NASH 导致药物胆汁排泄、全身浓度和肾脏处理的变化,在特定情况下会导致药物疗效或毒性的改变。未来的临床药物研究应关注这一特殊患者群体,以避免 NAFLD 患者发生严重的不良事件。

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