使用酶联免疫吸附测定法测定小鼠体内抗体的全身药代动力学及组织间隙浓度的推导。
Whole-Body Pharmacokinetics of Antibody in Mice Determined using Enzyme-Linked Immunosorbent Assay and Derivation of Tissue Interstitial Concentrations.
机构信息
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY, USA.
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY, USA.
出版信息
J Pharm Sci. 2021 Jan;110(1):446-457. doi: 10.1016/j.xphs.2020.05.025. Epub 2020 Jun 2.
Abstract
Here we have reported whole-body disposition of wild-type IgG and FcRn non-binding IgG in mice, determined using Enzyme-Linked Immunosorbent Assay (ELISA). The disposition data generated using ELISA are compared with previously published biodistribution data generated using radiolabelled IgG. In addition, we introduce a novel concept of ABC values, which are defined as percentage ratios of tissue interstitial and plasma AUC values. These values can help in predicting tissue interstitial concentrations of monoclonal antibodies (mAbs) based on the plasma concentrations. Tissue interstitial concentrations derived from our study are also compared with previously reported values measured using microdialysis or centrifugation method. Lastly, the new set of biodistribution data generated using ELISA are used to refine the PBPK model for mAbs.
摘要
在这里，我们使用酶联免疫吸附测定（ELISA）报告了野生型 IgG 和 FcRn 非结合 IgG 在小鼠体内的全身分布。使用 ELISA 生成的分布数据与先前使用放射性标记 IgG 生成的生物分布数据进行了比较。此外，我们引入了 ABC 值的新概念，它定义为组织间质和血浆 AUC 值的百分比比值。这些值可帮助根据血浆浓度预测单克隆抗体（mAb）的组织间质浓度。我们的研究中得出的组织间质浓度也与以前使用微透析或离心法测量的报告值进行了比较。最后，使用 ELISA 生成的新的生物分布数据集用于改进 mAb 的 PBPK 模型。
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