CoChat
Sign Up
Cited by 192Monoclonal and Polyclonal Antibodies ResearchPharmaceutical studies and practicesStatistical Methods in Clinical Trials

Fixed Dosing Versus Body Size—Based Dosing of Monoclonal Antibodies in Adult Clinical Trials

Wang, Diane D., Zhang, Shuzhong, Zhao, Hong, Men, Angela Y., Parivar, Kourosh·2009·The Journal of Clinical Pharmacology
DOI 10.1177/0091270009337512
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1177/0091270009337512

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Population pharmacokinetic modeling using data from clinical trials of various biotherapeutics has confirmed that fixed dosing of monoclonal antibodies could be feasible for the majority of molecules assessed, without impairing the safety and efficacy of the treatment.

    “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]

  • The average variability in AUC and Cmax of all 12 mAbs was similar following fixed dosing and bodyweight/body surface area-based dosing (AUC 42.4 versus 44.2%, Cmax 30.1 and 30.3%, respectively).

    “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]

  • There is evidence that fixed dosing of mAbs could generally be justified without impairing the safety and efficacy of the treatment.

    “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]

  • Wang et al. found that body size-based dosing and fixed dosing performed similarly across the 12 mAbs investigated in adult patients.

    “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]

  • Body size-adjusted administration resulted in lower pharmacokinetic variability for five mAbs, whereas fixed dosing resulted in lower pharmacokinetic variability for the other seven mAbs.

    “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]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

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.
ORCID
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
DOI
10.1177/0091270009337512
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
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1283 d)
Locations
  • The Journal of Clinical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review