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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Veröffentlicht in:Clinical pharmacokinetics Jg. 55; H. 7; S. 789 - 805
Hauptverfasser: Gill, Katherine L., Machavaram, Krishna K., Rose, Rachel H., Chetty, Manoranjenni
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Cham Springer International Publishing 01.07.2016
Springer Nature B.V
Schlagworte:
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
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Zusammenfassung: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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ISSN:0312-5963
1179-1926
1179-1926
DOI:10.1007/s40262-015-0361-4