Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Sandwich CT13 9NJ, UK.
Regul Toxicol Pharmacol. 2010 Jun;57(1):70-3. doi: 10.1016/j.yrtph.2010.01.001. Epub 2010 Jan 13.
Toxicokinetic data have traditionally been presented as maximum observed plasma concentrations (C(max)) and area under the concentration time curve (AUC) values. These values have been used to compare exposures across studies and species to provide valuable interpretation of drug safety data. Increasingly, questions are asked of toxicology studies to more accurately describe the concentration effect relationships in terms of compound affinity for target and off-target receptors. C(max) values can immediately be referenced to known pharmacological activities, particularly when the extent of plasma protein binding is taken into account. This provides a measure of the more pharmacologically relevant free drug exposure. AUC values on the other hand contain the component of time, which means that direct comparison to pharmacological activity values are not immediately possible. Conversion of AUC to average plasma concentration (C(av)) provides a simple and convenient means to allow such a comparison without losing any information imparted by AUC values. In this paper, the benefit and advantage of applying C(av) values is illustrated using examples taken from the literature.
毒代动力学数据通常以最大观测血浆浓度 (C(max)) 和浓度-时间曲线下面积 (AUC) 值呈现。这些值被用于比较不同研究和物种中的暴露情况，为药物安全性数据提供有价值的解释。越来越多的毒理学研究被要求更准确地描述化合物与靶标和非靶标受体亲和力的浓度效应关系。当考虑到血浆蛋白结合程度时，C(max) 值可以立即参考已知的药理学活性，特别是当涉及到程度时。这提供了更具药理学相关性的游离药物暴露的衡量标准。另一方面，AUC 值包含时间成分，这意味着不能直接将其与药理学活性值进行比较。将 AUC 转换为平均血浆浓度 (C(av)) 提供了一种简单方便的方法，可以在不丢失 AUC 值提供的任何信息的情况下进行这种比较。本文通过文献中的实例说明了应用 C(av) 值的益处和优势。
