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Absorption and Drug Development: Solubility, Permeability, and Charge State von Avdeef, Alex (eBook)

  • Erscheinungsdatum: 11.04.2012
  • Verlag: Wiley
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Absorption and Drug Development: Solubility, Permeability, and Charge State

Explains how to perform and analyze the results of the latest physicochemical methods With this book as their guide, readers have access to all the current information needed to thoroughly investigate and accurately determine a compound's pharmaceutical properties and their effects on drug absorption. The book emphasizes oral absorption, explaining all the physicochemical methods used today to analyze drug candidates. Moreover, the author provides expert guidance to help readers analyze the results of their studies in order to select the most promising drug candidates. This Second Edition has been thoroughly updated and revised, incorporating all the latest research findings, methods, and resources, including: Descriptions and applications of new PAMPA models, drawing on more than thirty papers published by the author's research group Two new chapters examining permeability and Caco-2/MDCK and permeability and the blood-brain barrier Expanded information and methods to support pKa determination New examples explaining the treatment of practically insoluble test compounds Additional case studies demonstrating the use of the latest physicochemical techniques New, revised, and expanded database tables throughout the book Well over 200 drawings help readers better understand difficult concepts and provide a visual guide to complex procedures. In addition, over 800 references serve as a gateway to the primary literature in the field, facilitating further research into all the topics covered in the book. This Second Edition is recommended as a reference for researchers in pharmaceutical R&D as well as in agrochemical, environmental, and other related areas of research. It is also recommended as a supplemental text for graduate courses in pharmaceutics. ALEX AVDEEF , PhD, is the founder of in-ADME Research. He has more than thirty years of experience in chemical instrumentation and software development. Internationally recognized as an authority in the field of solution chemistry, Dr. Avdeef has an extensive list of scholarly publications to his credit.

Produktinformationen

    Format: ePUB
    Kopierschutz: AdobeDRM
    Seitenzahl: 544
    Erscheinungsdatum: 11.04.2012
    Sprache: Englisch
    ISBN: 9781118286036
    Verlag: Wiley
    Größe: 34516 kBytes
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Absorption and Drug Development: Solubility, Permeability, and Charge State

NOMENCLATURE
A area of the PAMPA filter (cm2) C 0 aqueous concentration of the uncharged species (mol - cm−3) Cm ( x ) solute concentration inside of a membrane, at position x (mol - cm−3) solute concentration inside a membrane, at position x (mol cm−3) CR , CD receiver and donor aqueous solute concentration, respectively (mol - cm−3) D Lipid–water distribution pH-dependent function (also called the apparent partition coefficient) D aq ( Dm ) diffusivity of a solute in aqueous (membrane) solution (cm2 - s−1) diff difference between the partition coefficient of the uncharged and the charged species D MEM diffusivity of a solute inside a membrane (cm2 - s−1) D MEM/W pH-dependent membrane–water apparent partition coefficient (dimensionless) Double-Sink two sink conditions present: ionization and binding E (Δφ) function due to potential drop across the cell junction (dimensionless) f (0), f (+), f (−) molecule concentration fraction in the uncharged, positively charged and negatively charged forms, respectively F ( r HYD/ R ) Renkin molecular sieving function, dimensionless fraction in the range of 0 to 1 F pf cerebrovascular flow velocity of perfusion fluid (mL - g−1 - s−1 brain tissue) h membrane thickness (cm) h ABL, , thickness of the ABL (cm), at the receiver (R), donor (D) side, respectively total thickness of the ABL, equals hit a molecule with (a) confirmed activity from a primary assay, (b) a good profile in secondary assays, and (c) a confirmed structure hm membrane thickness (cm) , , excess lipid layer thicknesses (receiver/donor sides), and filter thickness total thickness of the lipid layers: in combo methodology where a measured property (e.g., PAMPA permeability coefficient) is additively "combined" with a calculated ( in silico ) descriptor (e.g., H-bond potential) J flux across a membrane (mol - cm−2 - s−1) j H low-pH junction potential parameter in the Avdeef–Bucher four-parameter electrode standardization equation j OH high-pH junction potential parameter in the Avdeef–Bucher four-parameter electrode standardization equation

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