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Clinical Pharmacology of Antibody-Drug Conjugates
Review

Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Antibody–Drug Conjugates (ADCs)

Mahmood Clinical Pharmacology Consultancy, LLC., Rockville, MD 20850, USA
Academic Editor: Jonas Helma-Smets
Received: 18 May 2021 / Revised: 1 July 2021 / Accepted: 11 October 2021 / Published: 15 October 2021
(This article belongs to the Special Issue Advances in Antibody–Drug Conjugates (ADCs))
Antibody–drug conjugates (ADCs) are complex molecules wherein a monoclonal antibody is linked to a biologically active drug (a small molecule), forming a conjugate. Initially, most of the ADCs were developed and are being developed for the treatment of cancer; however, with time, it has been realized that ADCs can also be developed to manage or cure other diseases. Pharmacokinetics (PK) plays an important role in modern-day drug development and the knowledge of PK is crucial in designing a safe and efficacious dose to treat a wide variety of diseases. There are several factors that can alter the PK of a drug; as a result, one has to adjust the dose in a patient population. These factors can be termed ‘intrinsic’ or ‘extrinsic’. For small molecules, the impact of both intrinsic and extrinsic factors is well established. The impact of age, gender, disease states such as renal and hepatic impairment, drug–drug interaction, food, and in many cases alcohol on the PK of small molecules are well known. On the other hand, for macromolecules, the impact of these factors is not well established. Since the ADCs are a combination product of a monoclonal antibody linked to a small molecule, both the small molecule and the monoclonal antibody of the ADCs may be subjected to many intrinsic and extrinsic factors. This review summarizes the impact of intrinsic and extrinsic factors on the PK of ADCs and the payloads. View Full-Text
Keywords: antibody–drug conjugates; pharmacokinetics; intrinsic and extrinsic factors; monoclonal antibodies; small molecule or payload antibody–drug conjugates; pharmacokinetics; intrinsic and extrinsic factors; monoclonal antibodies; small molecule or payload
MDPI and ACS Style

Mahmood, I. Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Antibody–Drug Conjugates (ADCs). Antibodies 2021, 10, 40. https://0-doi-org.brum.beds.ac.uk/10.3390/antib10040040

AMA Style

Mahmood I. Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Antibody–Drug Conjugates (ADCs). Antibodies. 2021; 10(4):40. https://0-doi-org.brum.beds.ac.uk/10.3390/antib10040040

Chicago/Turabian Style

Mahmood, Iftekhar. 2021. "Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Antibody–Drug Conjugates (ADCs)" Antibodies 10, no. 4: 40. https://0-doi-org.brum.beds.ac.uk/10.3390/antib10040040

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