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Potential Sources of Inter-Subject Variability in Monoclonal Antibody Pharmacokinetics

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Abstract

Understanding inter-subject variability in drug pharmacokinetics and pharmacodynamics is important to ensure that all patients attain suitable drug exposure to achieve efficacy and avoid toxicity. Inter-subject variability in the pharmacokinetics of therapeutic monoclonal antibodies (mAbs) is generally moderate to high; however, the factors responsible for the high inter-subject variability have not been comprehensively reviewed. In this review, the extent of inter-subject variability for mAb pharmacokinetics is presented and potential factors contributing to this variability are explored and summarised. Disease status, age, sex, ethnicity, body size, genetic polymorphisms, concomitant medication, co-morbidities, immune status and multiple other patient-specific details have been considered. The inter-subject variability for mAb pharmacokinetics most likely depends on the complex interplay of multiple factors. However, studies aimed at investigating the reasons for the inter-subject variability are sparse. Population pharmacokinetic models and physiologically based pharmacokinetic models are useful tools to identify important covariates, aiding in the understanding of factors contributing to inter-subject variability. Further understanding of inter-subject variability in pharmacokinetics should aid in development of dosing regimens that are more appropriate.

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    Katherine L. Gill, Krishna K. Machavaram, Rachel H. Rose & Manoranjenni Chetty

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Katherine L. Gill, Krishna K. Machavaram, Rachel H. Rose and Manoranjenni Chetty are employees of Simcyp (a Certara company) and declare no conflicts of interest that might be relevant to the contents of this manuscript.

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Gill, K.L., Machavaram, K.K., Rose, R.H. et al. Potential Sources of Inter-Subject Variability in Monoclonal Antibody Pharmacokinetics. Clin Pharmacokinet 55, 789–805 (2016). https://doi.org/10.1007/s40262-015-0361-4

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