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Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of 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 realize...

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Autor principal: Mahmood, Iftekhar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544203/
https://www.ncbi.nlm.nih.gov/pubmed/34698086
http://dx.doi.org/10.3390/antib10040040
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author Mahmood, Iftekhar
author_facet Mahmood, Iftekhar
author_sort Mahmood, Iftekhar
collection PubMed
description 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.
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spelling pubmed-85442032021-10-26 Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Antibody–Drug Conjugates (ADCs) Mahmood, Iftekhar Antibodies (Basel) Review 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. MDPI 2021-10-15 /pmc/articles/PMC8544203/ /pubmed/34698086 http://dx.doi.org/10.3390/antib10040040 Text en © 2021 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mahmood, Iftekhar
Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Antibody–Drug Conjugates (ADCs)
title Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Antibody–Drug Conjugates (ADCs)
title_full Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Antibody–Drug Conjugates (ADCs)
title_fullStr Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Antibody–Drug Conjugates (ADCs)
title_full_unstemmed Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Antibody–Drug Conjugates (ADCs)
title_short Effect of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Antibody–Drug Conjugates (ADCs)
title_sort effect of intrinsic and extrinsic factors on the pharmacokinetics of antibody–drug conjugates (adcs)
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544203/
https://www.ncbi.nlm.nih.gov/pubmed/34698086
http://dx.doi.org/10.3390/antib10040040
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