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• W2793279529 abstract "Fraction unbound (fu) of liver tissue, hepatocytes, and other cell types is an essential parameter used to estimate unbound liver drug concentration and intracellular free drug concentration. fu,liver and fu,cell are frequently measured in multiple species and cell types in drug discovery and development for various applications. A comparison study of 12 matrices for fu,liver and fu,cell of hepatocytes in five different species (mouse, rat, dog, monkey, and human), as well as fu,cell of Huh7 and human embryonic kidney 293 cell lines, was conducted for 22 structurally diverse compounds with the equilibrium dialysis method. Using an average bioequivalence approach, our results show that the average difference in binding to liver tissue, hepatocytes, or different cell types was within 2-fold of that of the rat fu,liver Therefore, we recommend using rat fu,liver as a surrogate for liver binding in other species and cell types in drug discovery. This strategy offers the potential to simplify binding studies and reduce cost, thereby enabling a more effective and practical determination of fu for liver tissues, hepatocytes, and other cell types. In addition, fu under hepatocyte stability incubation conditions should not be confused with fu,cell, as one is a diluted fu and the other is an undiluted fu Cell density also plays a critical role in the accurate measurement of fu,cell." @default.
• W2793279529 created "2018-03-29" @default.
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• W2793279529 date "2018-02-02" @default.
• W2793279529 modified "2023-10-12" @default.
• W2793279529 title "Comparison of Species and Cell-Type Differences in Fraction Unbound of Liver Tissues, Hepatocytes, and Cell Lines" @default.
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• W2793279529 doi "https://doi.org/10.1124/dmd.117.079152" @default.
• W2793279529 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29437874" @default.
• W2793279529 hasPublicationYear "2018" @default.
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