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
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.
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