Potential Sources of Inter-Subject Variability in Monoclonal Antibody Pharmacokinetics

• Published in: Clinical pharmacokinetics Vol. 55; no. 7; pp. 789 - 805
• Main Authors: Gill, Katherine L., Machavaram, Krishna K., Rose, Rachel H., Chetty, Manoranjenni
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.07.2016; Springer Nature B.V
• Subjects: Age Factors; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacokinetics; Body Weights and Measures; Comorbidity; Dose-Response Relationship, Drug; Drug Interactions; Ethnic Groups; Histocompatibility Antigens Class I - metabolism; Humans; Internal Medicine; Lymphatic System - metabolism; Medicine; Medicine & Public Health; Models, Biological; Pharmacology/Toxicology; Pharmacotherapy; Polymorphism, Genetic; Receptors, Fc - metabolism; Review Article; Severity of Illness Index; Sex Factors; Omalizumab; Alemtuzumab; Infliximab; Adalimumab; Rheumatoid Arthritis Patient
• ISSN: 0312-5963; 1179-1926; 1179-1926
• DOI: 10.1007/s40262-015-0361-4

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.