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

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 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.

Keywords: Antibody biodistribution coefficient; Antibody interstitial concentration; Antibody pharmacokinetics; ELISA; Neonatal Fc receptor (FcRn); Tissue biodistribution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Histocompatibility Antigens Class I / metabolism
  • Immunoglobulin G* / metabolism
  • Mice
  • Receptors, Fc / metabolism
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Receptors, Fc