Physiologically based pharmacokinetic modelling: a sub-compartmentalized model of tissue distribution

J Pharmacokinet Pharmacodyn. 2007 Dec;34(6):789-806. doi: 10.1007/s10928-007-9071-3. Epub 2007 Sep 25.

Abstract

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 differential 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 coefficients 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Models, Biological*
  • Pharmacokinetics*
  • Tissue Distribution