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Cited by 500Monoclonal and Polyclonal Antibodies ResearchBiosimilars and Bioanalytical MethodsPharmaceutical studies and practices

Population Pharmacokinetics of Therapeutic Monoclonal Antibodies

Dirks, Nathanael L., Meibohm, Bernd·2010·Clinical Pharmacokinetics
DOI 10.2165/11535960-000000000-00000
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Abstract

A growing number of population pharmacokinetic analyses of therapeutic monoclonal antibodies (mAbs) have been published in the scientific literature. The aims of this article are to summarize the findings from these studies and to relate the findings to the general pharmacokinetic and structural characteristics of therapeutic mAbs. A two-compartment model was used in the majority of the population analyses to describe the disposition of the mAb. Population estimates of the volumes of distribution in the central (V(1)) and peripheral (V(2)) compartments were typically small, with median (range) values of 3.1 (2.4-5.5) L and 2.8 (1.3-6.8) L, respectively. The estimated between-subject variability in the V(1) was usually moderate, with a median (range) coefficient of variation (CV) of 26% (12-84%). Between-subject variability in other distribution-related parameters such as the V(2) and intercompartmental clearance were often not estimated. Although the pharmacokinetic models used most frequently in the population analyses were models with linear clearance, other models with nonlinear, or parallel linear and nonlinear clearance pathways were also applied, as many therapeutic mAbs are eliminated via saturable target-mediated mechanisms. Population estimates of the maximum elimination rate (V(max)) and the mAb concentration at which elimination was at half maximum for Michaelis-Menten-type elimination pathways varied considerably among the different therapeutic mAbs. However, estimates of the total clearance (CL) of mAbs with linear clearance characteristics and of the clearance of mAbs via the linear clearance pathway (CL(L)) with parallel linear and nonlinear clearance were quite similar for the different mAbs and typically ranged from 0.2 to 0.5 L/day, which is relatively close to the estimated clearance of endogenous IgG of 0.21 L/day. The between-subject variability in the V(max), CL and CL(L) was moderate to high, with estimated CVs ranging from 15% to 65%. Measures of body size were the covariates most commonly identified as influencing the pharmacokinetics of therapeutic mAbs. In summary, many features of the population pharmacokinetics of currently used therapeutic mAbs are similar, despite differences in their pharmacological targets and studied patient populations.

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  • The FcRn-mediated recycling process is most likely responsible for the observed relatively long half-life of mAbs of 11-30 days in humans, which is similar to the half-life of endogenous IgG (~21 days).

    “This recycling process is most likely responsible for the observed relatively long half‐life of mAbs of 11–30 days in humans (Table 3), which is similar to the half‐life of endogenous IgG (∼21 days).31”

    From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [31]

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Authors
Dirks, N. L., & Meibohm, B.
Affiliations
University of Tennessee Health Science Center (US)
Corresponding author
Meibohm, Bernd
ORCID
Venue
Clinical Pharmacokinetics
Publisher
Springer Science and Business Media LLC
Published
2010-10
Volume
49
Issue
10
Pages
633-659
ISSN
0312-5963 (ISSN-L)
DOI
10.2165/11535960-000000000-00000
OpenAlex
W2067933166
Semantic Scholar
78f4e15f0fe1a9d2a7fede1aa15eb7d41741d661
Cited by
500
References
140
Citations by year
2026: 25 · 2025: 30 · 2024: 36 · 2023: 24 · 2022: 24 · 2021: 34 · 2020: 41 · 2019: 49 · 2018: 37 · 2017: 42 · 2016: 28 · 2015: 35 · 2014: 38 · 2013: 23 · 2012: 20
FWCI
2.51
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
therapeutic monoclonal antibodies, population pharmacokinetics, two-compartment model, between-subject variability, Michaelis-Menten elimination, IgG clearance, nonlinear clearance
MeSH terms
Antibodies, Monoclonal, Clinical Trials as Topic, Female, Humans, Male, Metabolic Clearance Rate, Structure-Activity Relationship

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