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Key Physicochemical Characteristics Influencing ADME Properties of Therapeutic Proteins

  • Xing JingEmail author
  • Yan Hou
  • William Hallett
  • Chandrahas G. Sahajwalla
  • Ping Ji
Chapter
  • 1.1k Downloads
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1148)

Abstract

Therapeutic proteins are a rapidly growing class of drugs in clinical settings. The pharmacokinetics (PK) of therapeutic proteins relies on their absorption, distribution, metabolism, and excretion (ADME) properties. Moreover, the ADME properties of therapeutic proteins are impacted by their physicochemical characteristics. Comprehensive evaluation of these characteristics and their impact on ADME properties are critical to successful drug development. This chapter summarizes all relevant physicochemical characteristics and their effect on ADME properties of therapeutic proteins.

Keywords

Protein therapeutics Physicochemical characteristics Pharmacokinetics (PK) ADME 

Abbreviations

ADA

Anti-drug antibody

ADC

Antibody drug conjugate

ADME

Absorption, distribution, metabolism, excretion

ASGPR

Asialoglycoprotein receptor

CD

Circular dichroism

cIEF

Capillary isoelectric focusing

DLS

Dynamic light scattering

DSC

Differential scanning calorimetry

DSF

Differential scanning fluorimetry

ECM

Extracellular matrix

Fab

Fragment antigen-binding domain

Fc

Fragment crystallizable domain

FcRn

Neonatal Fc receptor

FcγR

Fc gamma receptors

FDA

U.S. Food and Drug Administration

FRET

Förster resonance energy transfer

GlcNAc

N-acetylglucosamine

IgG

Immunoglobulin G

ITC

Isothermal titration calorimetry

mAb

Monoclonal antibody

ManR

Mannose receptor

MST

Microscale thermophoresis

MW

Molecular weight

PEG

Polyethylene glycol

pI

Isoelectric point

PK

Pharmacokinetics

SC

Subcutaneous

SPR

Surface plasmon resonance

T1/2

Half-life

Tmax

Time to peak concentration

TMDD

Target mediated drug disposition

TNF

Tumor necrosis factor

Vd

Volume of distribution

Notes

Acknowledgments

The authors sincerely thank the critical review of the chapter from Dr. Sarah Schrieber and Dr. Vitaliy Klimov from Office of Clinical Pharmacology, FDA.

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Xing Jing
    • 1
    Email author
  • Yan Hou
    • 1
  • William Hallett
    • 1
  • Chandrahas G. Sahajwalla
    • 1
  • Ping Ji
    • 1
  1. 1.U.S. Food and Drug Administration, Office of Clinical Pharmacology, DV IISilver SpringUSA

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