A model-based dependence of the human tissue/blood partition coefficients of chemicals on lipophilicity and tissue composition

Partitioning of up to thirty-six nonionizable chemicals between seven tissu es (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 accumulati on and protein binding of individual compounds was described as the Colland er-type function of their lipophilicity expressed by the 1-octanol/water pa rtition coefficients. The resulting model-based expression described satisf actorily the tissue/blood partition coefficients as a nonlinear function of lipophilicity and tissue composition (a standard content of lipids, protei ns, and water). The calibrated model is suitable for prediction of the tiss ue/blood partition coefficients for non-amphiphilic nonionizable chemicals with the 1-octanol/water partition coefficients varying between 0.01 and 10 0,000, i.e. practically in the whole range for which equilibrium tissue/blo od distribution can be used in physiologically based pharmacokinetic models .