Biomaterial Database

Physiologically based pharmacokinetic modelling: a sub-compartmentalized model of tissue distribution. 2007

Max von Kleist, and Wilhelm Huisinga

Department of Mathematics and Computer Science, and DFG Research Center Matheon, Freie Universität Berlin, Berlin, Germany.

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.

UI	MeSH Term	Description	Entries
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010599	Pharmacokinetics	Dynamic and kinetic mechanisms of exogenous chemical DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology.	ADME,ADME-Tox,ADMET,Absorption, Distribution, Metabolism, Elimination, and Toxicology,Absorption, Distribution, Metabolism, and Elimination,Drug Kinetics,Kinetics, Drug,LADMER,Liberation, Absorption, Distribution, Metabolism, Elimination, and Response
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014018	Tissue Distribution	Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.	Distribution, Tissue,Distributions, Tissue,Tissue Distributions