Potential Sources of Inter-Subject Variability in Monoclonal Antibody Pharmacokinetics

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 genera...

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Podrobná bibliografie
Vydáno v:	Clinical pharmacokinetics Ročník 55; číslo 7; s. 789 - 805
Hlavní autoři:	Gill, Katherine L., Machavaram, Krishna K., Rose, Rachel H., Chetty, Manoranjenni
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Cham Springer International Publishing 01.07.2016 Springer Nature B.V
Témata:	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
On-line přístup:	Získat plný text
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Popis
Shrnutí:	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.
Bibliografie:	SourceType-Scholarly Journals-1 ObjectType-General Information-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23
ISSN:	0312-5963 1179-1926 1179-1926
DOI:	10.1007/s40262-015-0361-4