The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Fixed Dosing Versus Body Size—Based Dosing of Monoclonal Antibodies in Adult Clinical Trials
Abstract
Although without clear scientific rationale, body size—based dosing is often used for administering monoclonal antibodies (mAbs). This simulation study compared the performance of body size—based and fixed dosing in reducing pharmacokinetic (PK) and/or pharmacodynamic (PD) variability in adults for 12 mAbs with published population PK and/or PD models. At the population level, 95th percentile intervals of concentration‐time profiles, distribution, and variability of exposure for 1000 subjects after both dosing approaches were examined. At the individual level, the difference between the exposures of patients with extreme body sizes from the typical exposure following both approaches was compared. The results show that the 2 dosing approaches perform similarly across the mAbs investigated with fixed dosing being better for some mAbs and body size—based dosing being better for the others. Based on this finding, we recommend using fixed dosing in first‐in‐human (FIH) adult studies because it offers other advantages. When sufficient data become available, a full assessment of body size effect on PK/PD should be conducted to determine the optimal dosing approach for phase 3 trials. Other factors that may affect the selection of dosing approach were also discussed. Dosing approach for mAbs in the pediatric population is out of the scope of this study.
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In the citing paper
“Furthermore, population pharmacokinetic (PopPK) modeling using data from clinical trials of various biotherapeutics has confirmed that fixed dosing of mAbs could be feasible for the majority of molecules assessed, without impairing the safety and efficacy of the treatment [20–23].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [20]
In the citing paper
“The average variability in area under the plasma concentration–time curve (AUC) and Cmax of all 12 mAbs was similar following the two dosing approaches (AUC 42.4 versus 44.2%, Cmax 30.1 and 30.3% by fixed dosing and bodyweight/body surface area-based dosing, respectively).”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [20]
In the citing paper
“Today, based on emerging knowledge about the pharmacokinetics of mAbs, considerable pharmacokinetic/pharmacodynamic data from clinical studies, and extensive PopPK modeling, there is evidence that fixed dosing of mAbs could generally be justified without impairing the safety and efficacy of the treatment [20, 23].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [20]
In the citing paper
“They found that the different dosing approaches performed similarly across the mAbs investigated.”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [20]
In the citing paper
“Body size-adjusted administration resulted in lower pharmacokinetic variability for five mAbs, whereas the pharmacokinetic variability of the other seven mAbs was lower with a fixed dosing approach.”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [20]
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Population Pharmacokinetics of Therapeutic Monoclonal Antibodies
Dirks, N. L., & Meibohm, B. (2010) · Clinical Pharmacokinetics · doi:10.2165/11535960-000000000-00000 · Cited by 500
Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities
Bittner, B., Richter, W., & Schmidt, J. (2018) · BioDrugs · doi:10.1007/s40259-018-0295-0 · Cited by 447
Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins
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Review of therapeutic drug monitoring of anticancer drugs part two – Targeted therapies
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Metadata
- Authors
- Wang, D. D., Zhang, S., Zhao, H., Men, A. Y., & Parivar, K.
- Affiliations
- Pfizer (United States) (US)
- United States Food and Drug Administration (US)
- Corresponding author
- Wang, Diane D.
- Venue
- The Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2009-09
- Volume
- 49
- Issue
- 9
- Pages
- 1012-1024
- ISSN
- 0021-9754 (ISSN-L)
- 0091-2700
- 1552-4604
- OpenAlex
- W2015186160
- Cited by
- 192
- References
- 29
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 5 · 2023: 9 · 2022: 14 · 2021: 11 · 2020: 18 · 2019: 20 · 2018: 11 · 2017: 17 · 2016: 8 · 2015: 13 · 2014: 15 · 2013: 10 · 2012: 7
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- monoclonal antibodies, fixed dosing, dose selection, pharmacokinetic variability, pharmacodynamic variability, exposure distribution
- MeSH terms
- Adult, Antibodies, Monoclonal, Body Surface Area, Body Weight, Clinical Trials as Topic, Computer Simulation, Dose-Response Relationship, Drug, Humans, Models, Biological
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