Clinical characteristics and circumstantial evidence suggest that idiosyncratic drug reactions are caused by reactive metabolites and are immune-mediated; however, there are few definitive data and there are likely exceptions. There are three principal hypotheses for how reactive metabolites might induce an immune-mediated idiosyncratic reaction: the hapten hypothesis, the danger hypothesis, and the PI hypothesis. It has been proposed that some idiosyncratic reactions, especially those involving the liver, represent metabolic idiosyncrasy; however, there are even less data to support this hypothesis. The unpredictable nature of these reactions makes mechanistic studies difficult. There is a very strong association with specific human leukocyte antigen (HLA) genes for certain reactions, but this has only been demonstrated for very few drugs. Animal models represent a very powerful tool for mechanistic studies, but the number of valid models is also limited. There may be biomarkers of risk; however, much more work needs to be done.

中文翻译：

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特异药物反应：目前的了解。

临床特征和环境证据表明，特异药物反应是由反应性代谢产物引起的，并且是免疫介导的。但是，确定的数据很少，并且可能会有例外。关于反应性代谢物如何诱导免疫介导的特异反应的三个主要假设：半抗原假设，危险假设和PI假设。有人提出某些特质反应，特别是涉及肝脏的特质反应代表代谢特质。但是，支持这一假设的数据甚至更少。这些反应的不可预测的性质使机理研究变得困难。某些反应与特定的人类白细胞抗原（HLA）基因有很强的联系，但这仅在极少数药物中得到证实。动物模型是用于机理研究的非常强大的工具，但是有效模型的数量也有限。可能存在危险的生物标志物；但是，还需要做更多的工作。