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- W2932792085 abstract "Abstract For preclinical and clinical assessment of therapeutically relevant unbound, free, brain concentrations, the pharmacokinetic parameter fraction of unbound drug in brain (f u,brain ) is commonly used to compensate total drug concentrations for nonspecific brain tissue binding (BTB). As, homogenous BTB is assumed between species and in health and disease, rat BTB is routinely used. The impact of Alzheimer’s disease (AD) on drug BTB in brain regions of interest (ROI), i.e., f u,brain,ROI , is yet unclear. This study for the first time provides insight into regional drug BTB and the validity of employing rat f u,brain,ROI as a surrogate of human BTB, by investigating five marketed drugs in post-mortem tissue from AD patients (n = 6) and age-matched controls (n = 6). Heterogeneous drug BTB was observed in all within group comparisons independent of disease and species. The findings oppose the assumption of uniform BTB, highlighting the need of case-by-case evaluation of f u,brain,ROI in translational CNS research." @default.
- W2932792085 created "2019-04-11" @default.
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- W2932792085 date "2019-03-29" @default.
- W2932792085 modified "2023-10-06" @default.
- W2932792085 title "Heterogeneous drug tissue binding in brain regions of rats, Alzheimer’s patients and controls: impact on translational drug development" @default.
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- W2932792085 doi "https://doi.org/10.1038/s41598-019-41828-4" @default.
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