Drug-Induced Hypersensitivity
Drug-Induced Hypersensitivity
复制标题
药物引起的超敏反应
DOI：
10.2165/00139709-200423040-00006
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
H. Ratajczak
中科院分区：
文献类型：
--
作者：
H. Ratajczak
药物诱导的超敏反应是一种不良反应，其特征是由用于预防、诊断或治疗的治疗剂量药物引发的破坏性免疫介导反应。免疫介导的药物超敏反应占药物不良反应的6-10%，在美国排在第四和第六位。报告的药物不良反应占所有药物不良反应的不到10%，因此问题的严重性是显著的，估计美国每年的成本超过300亿美元（1995年值）。此外，在药物开发的临床前阶段不确定药物产生超敏反应的潜力，成本可能会很高。据估计，每种药物的临床前阶段和临床I期、II期和III期费用分别约为600万美元、1200万美元、1200万美元和1亿美元（1999年值）。重要的是，在开发过程中尽可能早地识别可能产生超敏反应的研究药物。如果药物间相互作用是已知的，或者如果建立了结构-活性关系，药物的一些不良反应是可以避免的。然而，这些方法是不够的。药物诱导的超敏反应需要适当的动物模型，特别是因为超敏反应已被认为是导致药物退出市场的主要原因。能够预测药物的超敏反应至关重要。大多数过敏反应发生在特应性个体。同样，经历过其他超敏反应的患者更有可能发生复发性反应。因此，应考虑使动物易发生反应的动物模型，例如使用适当的佐剂和种属。使用不同规格的已知阳性对照品，研究者可以将阳性对照品作为标准品对反应进行分级。这种方法可能比使用新模型在更短的时间内产生更大的结果。为了最大的安全性，必须使用经过彻底验证的良好理解的模型。
Drug-induced hypersensitivity is an adverse reaction, characterised by damaging immune-mediated responses, initiated by medicine given at therapeutic doses for prevention, diagnosis or treatment. Immune-mediated drug hypersensitivity accounts for 6–10% of the adverse drug reactions, which rank between the fourth and sixth leading causes of death in the US. With <10% of all adverse drug reactions reported, the magnitude of the problem is significant, with estimates of costs >$US30 billion annually in the US (1995 value). In addition, the costs of not determining the potential of a drug to produce hypersensitivity in the pre-clinical phase of drug development can be substantial. It has been estimated that the pre-clinical phase and clinical phase I, phase II and phase III costs are approximately $US6 million, $US12 million, $US12 million and $US100 million per drug, respectively (1999 values). It is important that investigational drugs with the potential to produce hypersensitivity reactions be identified as early in the development process as possible. Some adverse reactions to drugs can be avoided if drug-drug interactions are known or if there is a structure-activity relationship established. However, these methods are inadequate. Appropriate animal models of drug-induced hypersensitivity are needed, especially because hypersensitivity has been cited as the leading reason for taking drugs off the market.It is of critical importance to be able to predict hypersensitivity reactions to drugs. Most anaphylactic reactions occur in atopic individuals. Similarly, patients who have experienced other hypersensitivity reactions are more likely to have recurrent reactions. Therefore, animal models should be considered that predispose the animal to the reaction, such as the use of appropriate adjuvants and species. Using known positive controls of varying strengths, the investigator can rank the reaction against the positive controls as standards. This approach might yield greater results in a shorter period of time than using novel models. For the greatest safety, use of well understood models that have been thoroughly validated is imperative.
影响因子：
120.7
作者：
Lasser, KE;Allen, PD;Bor, DH
通讯作者：
Bor, DH
C3a 受体在豚鼠全身过敏反应中的次要作用。
DOI：
10.1016/s0162-3109(99)00152-6
发表时间：
2000
期刊：
Immunopharmacology
影响因子：
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作者：
Regal,JF;Klos,A
通讯作者：
Klos,A