Clinical Pharmacokinetics

, Volume 58, Issue 2, pp 169–187 | Cite as

Influence of Antigen Mass on the Pharmacokinetics of Therapeutic Antibodies in Humans

  • David TernantEmail author
  • Nicolas Azzopardi
  • William Raoul
  • Theodora Bejan-Angoulvant
  • Gilles Paintaud
Review Article


Therapeutic antibodies are increasingly used to treat various diseases, including neoplasms and chronic inflammatory diseases. Antibodies exhibit complex pharmacokinetic properties, notably owing to the influence of antigen mass, i.e. the amount of antigenic targets to which the monoclonal antibody binds specifically. This review focuses on the influence of antigen mass on the pharmacokinetics of therapeutic antibodies quantified by pharmacokinetic modelling in humans. Out of 159 pharmacokinetic studies, 85 reported an influence of antigen mass. This influence led to non-linear elimination decay in 50 publications, which was described using target-mediated drug disposition or derived models, as quasi-steady-state, irreversible binding and Michaelis–Menten models. In 35 publications, the pharmacokinetics was apparently linear and the influence of antigen mass was described as a covariate of pharmacokinetic parameters. If some reported covariates, such as the circulating antigen level or tumour size, are likely to be correlated to antigen mass, others, such as disease activity or disease type, may contain little information on the amount of antigenic targets. In some cases, antigen targets exist in different forms, notably in the circulation and expressed at the cell surface. The influence of antigen mass should be soundly described during the early clinical phases of drug development. To maximise therapeutic efficacy, sufficient antibody doses should be administered to ensure the saturation of antigen targets by therapeutic antibodies in all patients. If necessary, antigen mass should be taken into account in routine clinical practice.


Compliance with Ethical Standards


This work was partly supported by the French Higher Education and Research Ministry under the program ‘Investissements d’avenir’ Grant Agreement: LabEx MAbImprove ANR-10-LABX-53-01.

Conflict of interest

David Ternant has given lectures for Amgen and Sanofi. Gilles Paintaud reports grants received by his research team, from Novartis, Roche Pharma, Sanofi-Genzyme, Chugai and Pfizer, outside of the submitted work. Theodora Bejan-Angoulvant, William Raoul and Nicolas Azzopardi have no conflicts of interest directly relevant to the content of this article.

Supplementary material

40262_2018_680_MOESM1_ESM.xlsx (346 kb)
Supplementary material 1 (XLSX 345 kb)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • David Ternant
    • 1
    • 2
    Email author
  • Nicolas Azzopardi
    • 1
  • William Raoul
    • 1
  • Theodora Bejan-Angoulvant
    • 1
    • 2
  • Gilles Paintaud
    • 1
    • 2
  1. 1.Université de Tours, EA7501 GICC, Team PATCHToursFrance
  2. 2.Department of Medical PharmacologyCHRU de Tours, Tours University HospitalTours CedexFrance

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