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Updated: Jul 30, 2025

Predicting In Vivo Payloads Delivery using a Blood-brain Tumor-barrier in a Dish
Published on: April 16, 2019
Interspecies evaluation of a physiologically based pharmacokinetic model to predict the biodistribution dynamics of
Christina Vasalou1, Joanna Harding2, Rhys D O Jones2
1Oncology R&D, AstraZeneca, Boston, Massachusetts, United States of America.
Abstract:
The exposure of a dendritic nanoparticle and its conjugated active pharmaceutical ingredient (API) was determined in mouse, rat and dog, with the aim of investigating interspecies differences facilitating clinical translation. Plasma area under the curves (AUCs) were found to be dose proportional across species, while dose normalized concentration time course profiles in plasma, liver and spleen were superimposable in mouse, rat and dog. A physiologically based pharmacokinetic (PBPK) model, previously developed for mouse, was evaluated as a suitable framework to prospectively capture concentration dynamics in rat and dog. The PBPK model, parameterized either by considering species-specific physiology or using alternate scaling methods such as allometry, was shown to capture exposure profiles across species. A sensitivity analysis highlighted API systemic clearance as a key parameter influencing released API levels. The PBPK model was utilized to simulate human exposure profiles, which overlaid dose-normalized data from mouse, rat and dog. The consistency in measured interspecies exposures as well as the capability of the PBPK model to simulate observed dynamics support its use as a powerful translational tool.
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