Journal
DRUG METABOLISM AND PHARMACOKINETICS
Volume 34, Issue 1, Pages 42-54Publisher
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.1016/j.dmpk.2018.11.001
Keywords
Pharmacokinetics; Peptide-drug conjugate; Antibody-drug conjugate; PEGylation; Radioimmunoconjugate; Immunotoxin; Albumin conjugates
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Funding
- NIGMS NIH HHS [R01 GM114179] Funding Source: Medline
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Protein and peptide conjugates have become an important component of therapeutic and diagnostic medicine. These conjugates are primarily designed to improve pharmacokinetics (PK) of those therapeutic or imaging agents, which do not possess optimal disposition characteristics. In this review we have summarized preclinical and clinical PK of diverse protein and peptide conjugates, and have showcased how different conjugation approaches are used to obtain the desired PK. We have classified the conjugates into peptide conjugates, non-targeted protein conjugates, and targeted protein conjugates, and have highlighted diagnostic and therapeutic applications of these conjugates. In general, peptide conjugates demonstrate very short half-life and rapid renal elimination, and they are mainly designed to achieve high contrast ratio for imaging agents or to deliver therapeutic agents at sites not reachable by bulky or non-targeted proteins. Conjugates made from non-targeted proteins like albumin are designed to increase the half-life of rapidly eliminating therapeutic or imaging agents, and improve their delivery to tissues like solid tumors and inflamed joints. Targeted protein conjugates are mainly developed from antibodies, antibody derivatives, or endogenous proteins, and they are designed to improve the contrast ratio of imaging agents or therapeutic index of therapeutic agents, by enhancing their delivery to the site-of-action. (c) 2018 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.
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