Tolvaptan Safety in Autosomal Dominant Polycystic Kidney Disease; Focus on Idiosyncratic Drug Induced Liver Injury Liabilities.

IF 3.4 3区 医学 Q2 TOXICOLOGY
Sean Hammond, Xiaoli Meng, Jane Barber, Merrie Mosedale, Amy Chadwick, Paul B Watkins, Dean J Naisbitt
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引用次数: 0

Abstract

Tolvaptan is a vasopressin V2 receptor antagonist which has proven to be an effective and mostly well-tolerated agent for the treatment of autosomal dominant polycystic kidney disease (ADPKD). However, its administration is associated with rare but serious idiosyncratic liver injury, which has warranted a black box warning on the drug labels and frequent monitoring of liver blood tests in the clinic. This review outlines mechanistic investigations that have been conducted to date and constructs a working narrative as explanation for the IDILI events that have occurred thus far. Potential risk factors which may contribute to individual susceptibility to DILI reactions are addressed, and key areas for future investigative/clinical development are highlighted.

托伐普坦在常染色体显性多囊肾病中的安全性;关注药物诱发的肝损伤责任。
托伐普坦是一种血管加压素V2受体拮抗剂,已被证明是治疗常染色体显性多囊肾病(ADPKD)的一种有效且耐受性良好的药物。然而,该药的用药与罕见但严重的特发性肝损伤有关,因此需要在药物标签上标注黑框警告,并在临床上频繁监测肝脏血液检测。本综述概述了迄今为止进行的机理研究,并对迄今为止发生的特发性肝损伤事件进行了解释。本综述探讨了可能导致个人易受 DILI 反应影响的潜在风险因素,并强调了未来研究/临床开发的关键领域。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Toxicological Sciences
Toxicological Sciences 医学-毒理学
CiteScore
7.70
自引率
7.90%
发文量
118
审稿时长
1.5 months
期刊介绍: The mission of Toxicological Sciences, the official journal of the Society of Toxicology, is to publish a broad spectrum of impactful research in the field of toxicology. The primary focus of Toxicological Sciences is on original research articles. The journal also provides expert insight via contemporary and systematic reviews, as well as forum articles and editorial content that addresses important topics in the field. The scope of Toxicological Sciences is focused on a broad spectrum of impactful toxicological research that will advance the multidisciplinary field of toxicology ranging from basic research to model development and application, and decision making. Submissions will include diverse technologies and approaches including, but not limited to: bioinformatics and computational biology, biochemistry, exposure science, histopathology, mass spectrometry, molecular biology, population-based sciences, tissue and cell-based systems, and whole-animal studies. Integrative approaches that combine realistic exposure scenarios with impactful analyses that move the field forward are encouraged.
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