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Understanding Inter-Individual Variability in Monoclonal Antibody Disposition


Understanding Inter-Individual Variability in Monoclonal Antibody Disposition

Veena A Thomas et al. Antibodies (Basel).


Monoclonal antibodies (mAbs) are currently the largest and most dominant class of therapeutic proteins. Inter-individual variability has been observed for several mAbs; however, an understanding of the underlying mechanisms and factors contributing to inter-subject differences in mAb disposition is still lacking. In this review, we analyze the mechanisms of antibody disposition and the putative mechanistic determinants of inter-individual variability. Results from in vitro, preclinical, and clinical studies were reviewed evaluate the role of the neonatal Fc receptor and Fc gamma receptors (expression and polymorphism), target properties (expression, shedding, turnover, internalization, heterogeneity, polymorphism), and the influence of anti-drug antibodies. Particular attention is given to the influence of co-administered drugs and disease, and to the physiological relevance of covariates identified by population pharmacokinetic modeling, as determinants of variability in mAb pharmacokinetics.

Keywords: co-administered drugs; disease; inter-subject variability; monoclonal antibodies; pharmacokinetics.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.


Figure 1
Figure 1
Evaluation of clinical trials for the most commonly identified significant covariates. The 100 clinical trials (phase I-III, years 2000–2018) that conducted population pharmacokinetic analysis were evaluated for the identified significant covariates. Bars represent the percentage of clinical trials that identified the variables- body weight/body surface area (BW/BSA, 82%), gender (18%), ADA (anti-drug antibody, 19%), creatinine clearance (CL, 7%), age (7%), disease activity (7%) and C-reactive protein (CRP, 7%) as a significant covariate.

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