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A Model-based Dependence of the Human Tissue/Blood Partition Coefficients of Chemicals on Lipophilicity and Tissue Composition

✍ Scribed by Baláž, Štefan ;Lukáčová, Viera

Publisher
John Wiley and Sons
Year
1999
Tongue
English
Weight
168 KB
Volume
18
Category
Article
ISSN
1611-020X

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✦ Synopsis

Partitioning of up to thirty-six nonionizable chemicals between seven tissues (fat, liver, brain, kidney, muscle, lung, heart) and blood in humans was modeled using membrane accumulation, protein binding, and distribution in the aqueous phases as relevant processes. The extent of membrane accumulation and protein binding of individual compounds was described as the Collander-type function of their lipophilicity expressed by the 1-octanolywater partition coef®cients. The resulting model-based expression described satisfactorily the tissueyblood partition coef®-cients as a nonlinear function of lipophilicity and tissue composition (a standard content of lipids, proteins, and water). The calibrated model is suitable for prediction of the tissueyblood partition coef®cients for non-amphiphilic nonionizable chemicals with the 1-octanolywater partition coef®cients varying between 0.01 and 100,000, i.e. practically in the whole range for which equilibrium tissueyblood distribution can be used in physiologically based pharmacokinetic models.

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