ADME Considerations and Bioanalytical Strategies for Pharmacokinetic Assessments of Antibody-Drug Conjugates

Overview

Journal Antibodies (Basel)

Date 2019 Sep 24

PMID 31544891

Citations 7

Authors

Si Mou

Yue Huang

Anton I Rosenbaum

Affiliations

Soon will be listed here.

Abstract

Antibody-drug conjugates (ADCs) are a unique class of biotherapeutics of inherent heterogeneity and correspondingly complex absorption, distribution, metabolism, and excretion (ADME) properties. Herein, we consider the contribution of various components of ADCs such as various classes of warheads, linkers, and conjugation strategies on ADME of ADCs. Understanding the metabolism and disposition of ADCs and interpreting exposure-efficacy and exposure-safety relationships of ADCs in the context of their various catabolites is critical for design and subsequent development of a clinically successful ADCs. Sophisticated bioanalytical assays are required for the assessments of intact ADC, total antibody, released warhead and relevant metabolites. Both ligand-binding assays (LBA) and hybrid LBA-liquid chromatography coupled with tandem mass spectrometry (LBA-LC-MS/MS) methods have been employed to assess pharmacokinetics (PK) of ADCs. Future advances in bioanalytical techniques will need to address the rising complexity of this biotherapeutic modality as more innovative conjugation strategies, antibody scaffolds and novel classes of warheads are employed for the next generation of ADCs. This review reflects our considerations on ADME of ADCs and provides a perspective on the current bioanalytical strategies for pharmacokinetic assessments of ADCs.

Citing Articles

Detailed Structural Elucidation of Antibody-Drug Conjugate Biotransformation Species Using High Resolution Multiple Reaction Monitoring Mass Spectrometry with Orthogonal Dissociation Methods.

Yang J, Tan H, Yuan J, Huang Y, Rosenbaum A ACS Pharmacol Transl Sci. 2025; 8(1):113-123.

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Development and validation of bioanalytical methods to support clinical study of disitamab vedotin.

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Development, Validation and Application of a Bridging ELISA for Detection of Antibodies against GQ1001 in Cynomolgus Monkey Serum.

Liu T, Sun Y, Deng X, Shi L, Chen W, Fang W Molecules. 2023; 28(4).

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Jin Y, Schladetsch M, Huang X, Balunas M, Wiemer A Pharmacol Ther. 2021; 229:107917.

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