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Predicting the Volume of Distribution of Drugs in Humans

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Recent studies have shown that many promising new drug candidates were abandoned due to poor pharmacokinetic properties (PKs). Therefore, it is important to predict the PKs of compounds during the early stages of drug development. The volume of distribution (VD) is one of the most important PK parameters. When considered along with systemic clearance, the VD determines the biological half-life, which is used for designing suitable dosage regimens and rational formulations. At present, the methods used to predict VD include (i) the extrapolation of animal data, (ii) physiologically based pharmacokinetic (PBPK) modeling and (iii) in silico approaches that employ quantitative structure - pharmacokinetic relationships (QSPR). In this article, the latest progress in the field of VD prediction is summarized in terms of the above three areas, respectively, and these approaches are expected to be valuable for screening new drugs during the early stages of drug discovery and development.





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Keywords: Physiologically based pharmacokinetic modeling; Quantitative structure-pharmacokinetic relationship; Tissue/plasma partition coefficients; Volume of distribution

Document Type: Research Article

Publication date: July 1, 2008

More about this publication?
  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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