Monoclonal Antibody Pharmacokinetics and Pharmacodynamics

  title={Monoclonal Antibody Pharmacokinetics and Pharmacodynamics},
  author={W. Wang and Eq Wang and JP Balthasar},
  journal={Clinical Pharmacology \& Therapeutics},
More than 20 monoclonal antibodies have been approved as therapeutic drugs by the US Food and Drug Administration, and it is quite likely that the number of approved antibodies will double in the next 7–10 years. Antibody drugs show several desirable characteristics, including good solubility and stability, long persistence in the body, high selectivity and specificity, and low risk for bioconversion to toxic metabolites. However, many antibody drugs demonstrate attributes that complicate drug… 

Pharmacokinetics, Pharmacodynamics and Physiologically-Based Pharmacokinetic Modelling of Monoclonal Antibodies

There is a clear need for more complex models to improve understanding of pharmacokinetic processes and pharmacodynamic interactions of mAbs with the immune system.

Pharmacokinetic Variability of Therapeutic Antibodies in Humans: A Comprehensive Review of Population Pharmacokinetic Modeling Publications

A quantitative overview of the occurrence of assessment and detection of the main covariates associated with monoclonal antibody pharmacokinetics is proposed by comprehensively examining all population pharmacokinetic studies of monoconal antibodies in humans.

Mechanisms Influencing the Pharmacokinetics and Disposition of Monoclonal Antibodies and Peptides

Monoclonal antibodies (mAbs) and peptides are an important class of therapeutic modalities that have brought improved health outcomes in areas with limited therapeutic optionality. Presently, there

Monoclonal antibodies: what are the pharmacokinetic and pharmacodynamic considerations for drug development?

This article discusses monoclonal antibodies with respect to their pharmacokinetics (including absorption, distribution and elimination) and their pharmacodynamics and looks at the pharmacokinetic/pharmacodynamic relationship, scaling from preclinical to clinical studies and selection of the first-in-human dose.

Therapeutic monoclonal antibody concentration monitoring: free or total?

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

This review focuses on the influence of antigen mass on the pharmacokinetics of therapeutic antibodies quantified by pharmacokinetic modelling in humans, which led to non-linear elimination decay in 50 publications.

Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions

The progress, challenges, and future directions in modeling antibody PK/PD are summarized and the potential of applying mechanistic models addressing the development questions is highlighted.

Pharmacokinetics/Pharmacodynamics and Disposition of Antibody-Drug Conjugates

The utility of pharmacokinetics–pharmacodynamics (PKPD) modeling is discussed in the context of providing guidance to assist in the successful development of these complex molecules.



Antibody pharmacokinetics and pharmacodynamics.

The U.S. Food and Drug administration has approved several polyclonal antibody preparations and at least 18 monoclonal antibody preparations (antibodies, antibody fragments, antibody fusion proteins, etc.) which are associated with several interesting pharmacokinetic characteristics.

The pharmacokinetics and pharmacodynamics of monoclonal antibodies--mechanistic modeling applied to drug development.

The pharmacology of therapeutic monoclonal antibodies is complex and dependant on both the structure of the antibody and the physiological system that it targets, and pharmacokinetic and pharmacodynamic modeling often plays a larger role during the development of therapeutic mAbs than for small molecules.

Antibodies as Carrier Proteins

This mini-review attempts to delineate the causal relation between the factors influencing antibody binding and the circulatory life of a therapeutic agent, be it a small drug or a macromolecule.

Pharmacokinetics of murine anti-human CD3 antibodies in man are determined by the disappearance of target antigen.

The pharmacokinetics and pharmacodynamics of an experimental therapeutic CD3 antibody, CLB-T3/4.A (murine IgA), given as a rejection treatment to renal transplant patients were to a great extent determined by antibody-induced changes in antigen in peripheral blood.

The Pharmacology of Monoclonal Antibodies a

A predictive pharmacology of biologicals must be based on theoretical and experimental information from several hierarchical levels: global, regional, local, cellular, and molecular, and here the authors will focus on one study of whole body pharmacokinetics, one development in regional delivery, and one issue at the local, or tissue, level.

Effect of target dynamics on pharmacokinetics of a novel therapeutic antibody against the epidermal growth factor receptor: implications for the mechanisms of action.

Receptor-mediated antibody internalization and degradation provides a saturable route of clearance that significantly affects pharmacokinetics, particularly at low antibody doses, as well as affecting the local mechanism of action.

Pharmacokinetics/Pharmacodynamics of Nondepleting Anti-CD4 Monoclonal Antibody (TRX1) in Healthy Human Volunteers

A receptor-mediated PK/PD model was developed to describe the dynamic interaction of TRX1 binding with CD4 receptors and this model was used to simulate PK/ PD time profiles after different dosing regimens to help guide the dose selection in future clinical studies.

Population Pharmacokinetics and Pharmacodynamics of the Anti-CD11a Antibody hu1124 in Human Subjects with Psoriasis

The pharmacokinetics of hu1124, a human anti-CD11a antibody, were investigated in human subjects with psoriasis and one of the receptor-mediated pharmacokinetic/pharmacodynamic models which was developed describes the dynamic interaction of hU1124 binding to CD11a, resulting in the removal of hi1124 from the circulation and reduction of cell surface CD 11a.

Potential and limitations of radioimmunodetection and radioimmunotherapy with monoclonal antibodies.

  • H. ZhuL. T. BaxterR. Jain
  • Biology, Medicine
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine
  • 1997
For radioimmunodetection, the most effective antibody form was the lower mol weight form, yet not sensitive enough for hepatic metastasis detection, and forRadioimmunotherapy, a relatively fast-clearing antibody form (F(ab')2 for ZCE025) in combination with long half-life beta(-)-emitters was optimal, yet inadequate as the sole therapeutic modality for solid tumors.