Whole-Body Pharmacokinetics of Antibody in Mice Determined using Enzyme-Linked Immunosorbent Assay and Derivation of Tissue Interstitial Concentrations

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 ABCIS 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. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

Automated summary

This study reports the whole-body disposition of wild-type IgG and FcRn non-binding IgG in mice, determined using ELISA. The concept of ABCIS values, the comparison with previously published biodistribution data, and the refinement of PBPK model for mAbs using the new set of biodistribution data generated using ELISA are highlighted in this study.