title: Potential Sources of Inter-Subject Variability in Monoclonal Antibody Pharmacokinetics.
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.
authors.affiliation: Simcyp (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU, UK.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Gill
authors.affiliation: Simcyp (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU, UK.
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Machavaram
authors.affiliation: Simcyp (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU, UK.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Rose
authors.affiliation: Simcyp (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU, UK. manoranjenni.chetty@certara.com.
authors.forename: Manoranjenni
authors.initials: M
authors.lastname: Chetty
mesh_terms: D000367:Age Factors; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics*; D001837:Body Weights and Measures; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005006:Ethnicity; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008208:Lymphatic System / Q000378:metabolism; D008954:Models, Biological; D011110:Polymorphism, Genetic; D011961:Receptors, Fc / Q000378:metabolism; D012720:Severity of Illness Index; D012737:Sex Factors
chemical_list: D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; C100688:Fc receptor, neonatal
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