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

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_IS 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.

SUBMITTER: Chang HP

PROVIDER: S-EPMC7708505 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Chang Hsuan-Ping HP Kim Se Jin SJ Shah Dhaval K DK

Journal of pharmaceutical sciences 20200602 1

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<sub>IS</sub> values, which are defined as percentage ratios of tissue interstitial and plasma AUC values. These values can help in predicting tissue intersti ...[more]

PMID: 32502472

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