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Physiologically Based Pharmacokinetic Modelling: A Sub-Compartmentalized Model of Tissue Distribution

von Kleist, Max and Huisinga, Wilhelm (2007) Physiologically Based Pharmacokinetic Modelling: A Sub-Compartmentalized Model of Tissue Distribution. Journal of Pharmacokinetics and Pharmacodynamics, 34 (6). pp. 789-806. ISSN 1573-8744

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We present a sub-compartmentalized model of drug distribution in tissue that extends existing approaches based on the well-stirred tissue model. It is specified in terms of di®erential equations that explicitly account for the drug concentration in erythrocytes, plasma, interstitial and cellular space. Assuming, in addition, steady state drug distribution and by lumping the different sub-compartments, established models to predict tissue-plasma partition coe±cients can be derived in an intriguingly simple way. This direct link is exploited to explicitly construct and parameterize the sub-compartmentalized model for moderate to strong bases, acids, neutrals and zwitterions. The derivation highlights the contributions of the different tissue constituents and provides a simple and transparent framework for the construction of novel tissue distribution models.

Item Type: Article
Keywords: Lumped tissue distribution models; Partition coefficients; PBPK; PK/PD; Mechanistic modelling; Unbound fraction; Hamilaton Institute.
Subjects: Science & Engineering > Biology
Science & Engineering > Hamilton Institute
Item ID: 1881
Identification Number: 0.1007/s10928-007-9071-3
Depositing User: Hamilton Editor
Date Deposited: 08 Mar 2010 14:00
Journal or Publication Title: Journal of Pharmacokinetics and Pharmacodynamics
Publisher: Springer Netherlands
Refereed: Yes

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