Physiologically based pharmacokinetic model of XXXX disposition in @entity35 following administration of deoxycholate formulation ( @entity2379  ): pooled analysis of published data.

@entity1 @entity8 @entity2379 @entity19 @entity35 @entity11015
The time course of tissue distribution of @entity2379 ( @entity11015 ) has not been sufficiently characterized despite its therapeutic importance and an apparent disconnect between plasma pharmacokinetics and clinical outcomes. The goals of this work were to develop and evaluate a physiologically based pharmacokinetic (PBPK) model to characterize the disposition properties of @entity11015 administered as deoxycholate formulation in healthy @entity35 and to examine the utility of the PBPK model for interspecies scaling of @entity11015 pharmacokinetics. @entity11015 plasma and tissue concentration-time data, following single and multiple intravenous administration of @entity2379   to @entity35 , from several publications were combined for construction of the model. Physiological parameters were fixed to literature values. Various structural models for single organs were evaluated, and the whole-body PBPK model included liver, spleen, kidney, lung, heart, gastrointestinal tract, plasma, and remainder compartments. The final model resulted in a good simultaneous description of both single and multiple dose data sets. Incorporation of three subcompartments for @entity8 was required for capturing a prolonged half-life in these organs. The predictive performance of the final PBPK model was assessed by evaluating its utility in predicting pharmacokinetics of @entity11015 in @entity19 and @entity1 . Clearance and permeability-surface area terms were scaled with body weight. The model demonstrated good predictions of plasma @entity11015 concentration-time profiles for both species. This modeling framework represents an important basis that may be further utilized for characterization of formulation- and disease-related factors in @entity11015 pharmacokinetics and pharmacodynamics.
