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• W2038026577 endingPage "344" @default.
• W2038026577 startingPage "321" @default.
• W2038026577 abstract "Volume of drug distribution is a primary pharmacokinetic parameter. This study assessed effects of drugs’ plasma protein binding and tissue distribution on volume of drug distribution and identified the most appropriate ways for its calculation. Effects of the distribution factors on the unbound and total drug plasma concentrations and on the corresponding volumes of distribution were studied using pharmacokinetic modeling and simulation approach based on in vitro and in vivo concentration vs. time data of diazepam, a model drug with extensive plasma protein binding and tissue distribution. Pharmacokinetics of diazepam were appropriately described by three-compartment pharmacokinetic model that incorporated the processes of plasma protein binding and tissue permeation. According to this model, displacement of the drug from plasma proteins increases the unbound (but not the total) plasma concentrations and induces faster drug elimination from the body. The distribution pattern of the drug in the body and the time course of unbound (pharmacologically active) drug concentrations correlated with the unbound volumes of distribution, but not with the total volumes of distribution. In conclusion, unbound volumes of distribution appropriately describe the drug distribution pattern and the time course of unbound drug concentrations and are recommended for use as primary pharmacokinetic parameters in pharmaceutical research." @default.
• W2038026577 created "2016-06-24" @default.
• W2038026577 creator A5004605882 @default.
• W2038026577 date "1981-01-01" @default.
• W2038026577 modified "2023-09-23" @default.
• W2038026577 title "Kinetics of drug-drug interactions" @default.
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• W2038026577 doi "https://doi.org/10.1016/0163-7258(81)90031-0" @default.
• W2038026577 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/7034002" @default.
• W2038026577 hasPublicationYear "1981" @default.
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