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 generally moderate to high; however, the factors responsible for the high inter-subject variability have not been comprehensively reviewed. In […]

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A Bottom-Up Whole-Body Physiologically Based Pharmacokinetic Model to Mechanistically Predict Tissue Distribution and the Rate of Subcutaneous Absorption of Therapeutic Proteins

The ability to predict subcutaneous (SC) absorption rate and tissue distribution of therapeutic proteins (TPs) using a bottom-up approach is highly desirable early in the drug development process prior to clinical data being available. A whole-body physiologically based pharmacokinetic (PBPK) model, requiring only a few drug parameters, to predict plasma and interstitial fluid concentrations of […]

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Are Physiologically Based Pharmacokinetic Models Reporting the Right Cmax? Central Venous Versus Peripheral Sampling Site.

Physiologically¬†based¬†pharmacokinetic¬†(PBPK)¬†models¬†can over-predict maximum plasma concentrations (Cmax) following intravenous administration. A proposed explanation is that invariably PBPK¬†models¬†report the concentration in the¬†central¬†venous¬†compartment, rather than the¬†site¬†where the samples are drawn. The purpose of this study was to identify and validate potential corrective¬†models¬†based¬†on anatomy and physiology governing the blood supply at the¬†site¬†of¬†sampling¬†and incorporate them into a PBPK platform. Four¬†models¬†were […]

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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 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 […]

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