Preclinical Pharmacokinetic Considerations for the Development of Antibody Drug Conjugates

Antibody drug conjugates (ADCs) are an emerging new class of targeted therapeutics for cancer that use antibodies to deliver cytotoxic drugs to cancer cells. There are two FDA approved ADCs on the market and over 30 ADCs in the clinical pipeline against a number of different cancer types. The struct...

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Bibliographic Details
Published in:Pharmaceutical research 2015-11, Vol.32 (11), p.3470-3479
Main Authors: Kamath, Amrita V., Iyer, Suhasini
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal - pharmacokinetics
Antibodies, Monoclonal - pharmacology
Antineoplastic Agents - adverse effects
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
Biochemistry
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Biotransformation
Cancer
Dose-Response Relationship, Drug
Drug Discovery - methods
Drug Evaluation, Preclinical
Drug therapy
Expert Review
FDA approval
Humans
Immunoconjugates - adverse effects
Immunoconjugates - pharmacokinetics
Immunoconjugates - pharmacology
Immunoglobulins
Kinetics
Medical Law
Molecular Targeted Therapy
Pharmacology/Toxicology
Pharmacy
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Summary:Antibody drug conjugates (ADCs) are an emerging new class of targeted therapeutics for cancer that use antibodies to deliver cytotoxic drugs to cancer cells. There are two FDA approved ADCs on the market and over 30 ADCs in the clinical pipeline against a number of different cancer types. The structure of an ADC is very complex with multiple components and considerable efforts are ongoing to determine the attributes necessary for clinical success. Understanding the pharmacokinetics of an ADC and how it impacts efficacy and toxicity is a critical part of optimizing ADC design and delivery i.e., dose and schedule. This review discusses the pharmacokinetic considerations for an ADC and tools and strategies that can be used to evaluate molecules at the preclinical stage.
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-014-1584-z