Clinical Pharmacokinetics of Therapeutic Monoclonal Antibodies

Keizer, Ron J.; Huitema, Alwin D.R.; Schellens, Jan H.M.; Beijnen, Jos H.

doi:10.2165/11531280-000000000-00000

Cited by 725Monoclonal and Polyclonal Antibodies ResearchBiosimilars and Bioanalytical MethodsPharmaceutical studies and practices

Clinical Pharmacokinetics of Therapeutic Monoclonal Antibodies

Keizer, Ron J., Huitema, Alwin D.R., Schellens, Jan H.M., Beijnen, Jos H.·2010·Clinical Pharmacokinetics

DOI 10.2165/11531280-000000000-00000

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Abstract

Monoclonal antibodies (mAbs) have been used in the treatment of various diseases for over 20 years and combine high specificity with generally low toxicity. Their pharmacokinetic properties differ markedly from those of non-antibody-type drugs, and these properties can have important clinical implications. mAbs are administered intravenously, intramuscularly or subcutaneously. Oral administration is precluded by the molecular size, hydrophilicity and gastric degradation of mAbs. Distribution into tissue is slow because of the molecular size of mAbs, and volumes of distribution are generally low. mAbs are metabolized to peptides and amino acids in several tissues, by circulating phagocytic cells or by their target antigen-containing cells. Antibodies and endogenous immunoglobulins are protected from degradation by binding to protective receptors (the neonatal Fc-receptor [FcRn]), which explains their long elimination half-lives (up to 4 weeks). Population pharmacokinetic analyses have been applied in assessing covariates in the disposition of mAbs. Both linear and nonlinear elimination have been reported for mAbs, which is probably caused by target-mediated disposition. Possible factors influencing elimination of mAbs include the amount of the target antigen, immune reactions to the antibody and patient demographics. Bodyweight and/or body surface area are generally related to clearance of mAbs, but clinical relevance is often low. Metabolic drug-drug interactions are rare for mAbs. Exposure-response relationships have been described for some mAbs. In conclusion, the parenteral administration, slow tissue distribution and long elimination half-life are the most pronounced clinical pharmacokinetic characteristics of mAbs.

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Both serum- and mAb-based therapeutics are costly to produce, store, and deliver as they require a cold supply chain and are often administered intravenously.
“both serum‐ and mAb‐based therapeutics are costly to produce, store, and deliver as they require a cold supply chain and are often administered intravenously (Chames et al, 2009; Keizer et al, 2010).”
From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Keizer et al, 2010

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Authors: Keizer, R. J., Huitema, A. D. R., Schellens, J. H. M., & Beijnen, J. H.
Affiliations: Slotervaartziekenhuis (NL)
Utrecht University (NL)
Corresponding author: Keizer, Ron J.
ORCID: Keizer, Ron J.
Huitema, Alwin D.R.
Schellens, Jan H.M.
Beijnen, Jos H.
Venue: Clinical Pharmacokinetics
Publisher: Springer Science and Business Media LLC
Published: 2010-08
Volume: 49
Issue: 8
Pages: 493-507
ISSN: 0312-5963 (ISSN-L)
DOI: 10.2165/11531280-000000000-00000
OpenAlex: W2059050919
Cited by: 725
References: 111
Citations by year: 2026: 36 · 2025: 48 · 2024: 54 · 2023: 63 · 2022: 46 · 2021: 67 · 2020: 47 · 2019: 59 · 2018: 58 · 2017: 55 · 2016: 37 · 2015: 52 · 2014: 40 · 2013: 26 · 2012: 24
FWCI: 2.90
Type: journal article
Language: en
Open access: closed
Locations: Clinical Pharmacokinetics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords: monoclonal antibodies, pharmacokinetics, neonatal Fc receptor, elimination half-life, nonlinear elimination, population pharmacokinetics, drug-drug interactions, exposure-response relationship, tissue distribution, clearance
MeSH terms: Absorption, Animals, Antibodies, Monoclonal, Drug Administration Routes, Drug Interactions, Humans, Immunologic Factors, Tissue Distribution, Mice, Knockout, Mice

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Clinical Pharmacokinetics of Therapeutic Monoclonal Antibodies

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