Drug-induced liver injury.
Drug-induced liver injury.
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DOI：
10.1007/978-3-642-00663-0_1
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发表时间：
2010-01-01
影响因子：
--
通讯作者：
Ju, Cynthia
中科院分区：
文献类型：
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作者：
Holt, Michael;Ju, Cynthia
许多药物和环境化学品都能引起一定程度的肝脏损伤。肝脏是药物不良反应的主要靶点，因为它在生物转化和排泄外来化合物方面发挥着核心作用，它在循环中的门户位置使其暴露于各种物质，以及它的解剖和生理结构。药物性肝损伤(DILI)仍然是导致候选药物失败或退出市场的最常见的不良指征。然而，DILI的绝对发病率很低，这对机械学研究提出了挑战。帝力仍然不可预测，这使得预防变得非常困难。在这一章中，我们将重点介绍对帝力的现有认识。我们首先对DILI的意义和流行病学进行概述，然后检查与DILI相关的临床表现和易感因素。随后回顾了目前关于DILI发病机制的文献，其中涉及直接影响细胞功能或引起免疫反应的药物或药物的反应性代谢物的参与。我们希望，本章将阐明与帝力有关的主要问题，涉及制药业、药品监管机构、医生和药剂师以及患者。
Many drugs and environmental chemicals are capable of evoking some degree of liver injury. The liver represents a primary target for adverse drug reactions due to its central role in biotransformation and excretion of foreign compounds, its portal location within the circulation exposing it to a wide variety of substances, and its anatomic and physiologic structure. Drug-induced liver injury (DILI) remains the single most common adverse indication leading to drug candidate failure or withdrawal from the market. However, the absolute incidence of DILI is low, and this presents a challenge to mechanistic studies. DILI remains unpredictable making prevention very difficult. In this chapter, we focus on the current understanding of DILI. We begin with an overview regarding the significance and epidemiology of DILI and then examine the clinical presentation and susceptibility factors related to DILI. This is followed by a review of the current literature regarding the proposed pathogenesis of DILI, which involves the participation of a drug, or most often a reactive metabolite of the drug, that either directly affects cellular function or elicits an immune response. It is our hope that this chapter will shed light on the major problems associated with DILI in regards to the pharmaceutical industry, drug regulatory agencies, physicians and pharmacists, and patients.