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    Evaluation of different in vitro surrogates to represent nonspecific binding for tissue: plasma water partition coefficient predictions

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    Genre
    Thesis/Dissertation
    Date
    2019
    Author
    Holt, Kimberly
    Advisor
    Korzekwa, Kenneth
    Committee member
    Korzekwa, Kenneth
    Nagar, Swati
    Childers, Wayne E.
    Barrero, Carlos A.
    Gibson, Christopher
    Department
    Pharmaceutical Sciences
    Subject
    Pharmaceutical Sciences
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/1455
    
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    DOI
    http://dx.doi.org/10.34944/dspace/1437
    Abstract
    With the growing use of physiologically-based pharmacokinetic (PBPK) modeling to predict the pharmacokinetics of a drug, accurate prediction of the tissue: plasma water partition coefficients (Kp,m) has become increasingly important. In these predictions, drug-lipid interactions have been traditionally described using the octanol: water partition coefficient (logP) and the vegetable: oil: water partition coefficient (logPvo). However, the logP does not fully represent all of the drug interactions with phospholipids, while the logPvo is calculated from the logP and not determined experimentally. Partitioning into microsomes has been used as a potential surrogate for phospholipid partitioning in our previous steady-state volume of distribution prediction method. Microsomal partitioning is able to act as a total phospholipid partitioning term, representing both acidic and neutral phospholipid interactions. Partitioning into adipocytes potentially can provide an alternative surrogate for d
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