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易感性的变异性——有多大,多频繁,对哪些药物产生哪些反应?

Variability in susceptibility - how big, how often, for what responses to what agents?

出版信息

Environ Toxicol Pharmacol. 1996 Oct 15;2(2-3):135-45. doi: 10.1016/S1382-6689(96)00044-0.

Abstract

This paper surveys some recent available observations in humans on interindividual variability in exposure-related parameters, pharmacokinetics, and pharmacodynamics. Overall, I think two inferences are warranted. First, the drug and epidemiological literatures do contain information that can shed new light on the extent of variability in the doses associated with different non-cancer responses. These data are waiting to be systematically extracted and analyzed. Second, I think it is likely that with more systematic measurement and analysis of interindividual variability we are likely to find that there are systematic tendencies for some kinds of responses to some categories of agents to occur at more variable exposures/doses than others. If we gather and analyze additional data of this type, we may be able to recommend adaptive modifications to the ten-fold safety factor tuned to these differences.

摘要

本文调查了一些最近在人类中获得的关于暴露相关参数、药代动力学和药效动力学个体间变异性的观察结果。总的来说,我认为有两个推论是合理的。首先,药物和流行病学文献确实包含了可以揭示与不同非癌症反应相关的剂量变异性程度的新信息。这些数据有待系统地提取和分析。其次,我认为,随着对个体间变异性的更系统的测量和分析,我们很可能会发现,对于某些种类的反应,某些类别的药物在更可变的暴露/剂量下发生的系统性趋势比其他药物更大。如果我们收集和分析更多此类类型的数据,我们可能能够根据这些差异,建议对针对这些差异进行调整的十倍安全系数进行适应性修改。

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