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020    9781118770320|q(electronic bk.) 
020    |z9781118152126 
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050  4 RM301.25 .V325 2013 
082 0  615.19 
100 1  Valko, Klara 
245 10 Physicochemical and Biomimetic Properties in Drug 
       Discovery :|bChromatographic Techniques for Lead 
       Optimization 
250    1st ed 
264  1 Somerset :|bJohn Wiley & Sons, Incorporated,|c2014 
264  4 |c©2014 
300    1 online resource (453 pages) 
336    text|btxt|2rdacontent 
337    computer|bc|2rdamedia 
338    online resource|bcr|2rdacarrier 
505 0  Intro -- PHYSICOCHEMICAL AND BIOMIMETIC PROPERTIES IN DRUG
       DISCOVERY: Chromatographic Techniques for Lead 
       Optimization -- Copyright -- CONTENTS -- Preface -- 1 The 
       Drug Discovery Process -- Summary -- Question for Review -
       - References -- 2 Drug-Likeness and Physicochemical 
       Property Space of Known Drugs -- Summary -- Questions for 
       Review -- References -- 3 Basic Pharmacokinetic Properties
       -- Absorption -- Plasma Protein Binding -- Distribution --
       Volume of Distribution -- Unbound Volume of Distribution -
       - Half-Life -- Metabolism and Clearance -- Free Drug 
       Hypothesis -- Summary -- Questions for Review -- 
       References -- 4 Principles and Methods of Chromatography 
       for the Application of Property Measurements -- 
       Theoretical Background of Chromatography -- Retention 
       Factor and Its Relation to the Distribution Constant 
       Between the Mobile and the Stationary Phases -- Measure of
       Separation Efficiency -- Resolution and Separation Time --
       Gradient Elution -- Applicability of Chromatography for 
       Measurements of Molecular Properties -- Summary -- 
       Questions for Review -- References -- 5 Molecular 
       Physicochemical Properties that Influence Absorption and 
       Distribution-Lipophilicity -- Partition Coefficient -- 
       Lipophilicity Measurements by Reversed Phase 
       Chromatography with Isocratic Elution -- Lipophilicity 
       Measurements by Reversed Phase Chromatography with 
       Gradient Elution -- Typical Measurement Condition for 
       Lipophilicity Determination by Reversed Phase Gradient 
       HPLC -- Lipophilicity of Charged Molecules-pH Dependenceof
       Lipophilicity -- Biomimetic Lipophilicity Measurements by 
       Chromatography -- Immobilized Human Serum Albumin (HSA) 
       Stationary Phase -- Typical Measurement Conditions of HSA 
       Binding by HPLC Retention -- Immobilized   -1-Acid-
       glycoprotein (AGP) Stationary Phase -- Typical Measurement
       Conditions of AGP Binding by HPLC Retention 
505 8  Immobilized Artificial Membrane (IAM) Stationary Phase -- 
       Typical Measurement Conditions of IAM Binding by HPLC 
       Retention -- Comparing Various Lipophilicity Measures by 
       the Solvation Equation Model -- Summary -- Questions for 
       Review -- References -- 6 Molecular Physicochemical 
       Properties that Influence Absorption and Distribution-
       Solubility -- Definition of Solubility -- Molecular 
       Interactions with Water -- Various Solubility Measurements
       that can be Applied During the Drug Discovery Process -- 
       Conditions that Affect Solubility -- Solubility-pH Profile
       -- Solubility and Dissolution in Biorelevant Media -- 
       Composition of Fasted State Simulated Intestinal Fluid 
       (FaSSIF) -- Preparation of FaSSIF Solution -- Composition 
       of Fed State Simulated Intestinal Fluid (FeSSIF) -- 
       Preparation of FeSSIF solution -- Summary -- Questions for
       Review -- References -- 7 Molecular Physicochemical 
       Properties that Influence Absorption and Distribution-
       Permeability -- Biological Membranes -- Artificial 
       Membranes -- Physicochemical Principles of Permeability --
       Experimental Methods to Measure Artificial Membrane 
       Permeability -- Relationships Between Permeability, 
       Lipophilicity, and Solubility -- Chromatography as a 
       Potential Tool for Measuring the Rate of Permeation -- 
       Summary -- Questions for Review -- References -- 8 
       Molecular Physicochemical Properties that 
       InfluenceAbsorption and Distribution-Acid 
       DissociationConstant-pKa -- Definition of pKa -- Methods 
       for Determining pKa -- Potentiometric Titration for the 
       Determination of pKa -- Spectrophotometric Determination 
       of pKa -- Determination of pKa by Capillary 
       Electrophoresis -- Chromatographic Approaches for the 
       Determination of pKa -- Summary -- Questions for Review --
       References -- 9 Models with Measured Physicochemical and 
       Biomimetic Chromatographic Descriptors-Absorption -- 
       Lipinski Rule of Five 
505 8  Absorption Models with Lipophilicity and Size -- 
       Biopharmaceutics Classification System (BCS) -- Absorption
       Potential-Maximum Absorbable Dose -- Abraham Solvation 
       Equations for Modeling Absorption -- Effect of Active 
       Transport and Metabolizing Enzymes on Oral Absorption and 
       Bioavailability -- Summary -- Questions for Review -- 
       References -- 10 Models with Measured Physicochemical and 
       Biomimetic Chromatographic Descriptors-Distribution -- 
       Models for Volume of Distribution -- Plasma Protein 
       Binding -- Blood/Brain Distributions -- Tissue 
       Distribution -- Summary -- Questions for Review -- 
       References -- 11 Models with Measured Physicochemical and 
       Biomimetic Chromatographic Descriptors-Drug Efficiency -- 
       Drug Efficiency -- Summary -- Questions for Review -- 
       References -- 12 Applications and Examples in Drug 
       Discovery -- Structure-Lipophilicity Relationships -- 
       Structure-Solubility Relationships -- Structure-
       Permeability Relationships -- Structure-Charge State 
       Relationships -- Structure-Protein Binding Relationships -
       - Structure-Phospholipid Binding Relationships -- Summary 
       -- Questions for Review -- References -- Appendix A 
       Answers to the Questions for Review -- Appendix B List of 
       Abbreviations and Symbols -- Index -- Supplemental Images 
520    KLARA VALKO is an Investigator in the Analytical Chemistry
       Department of Molecular Discovery Research at 
       GlaxoSmithKline. Dr. Valko has more than thirty years of 
       experience in HPLC, GC, and LC/MS. She also has more than 
       ten years of experience teaching physicochemical 
       measurements and ADME optimization tools at the UCL School
       of Pharmacy. Currently, Dr. Valko is an Honorary Professor,
       leading the Physchem/ADME module for a drug discovery MSc 
       course 
588    Description based on publisher supplied metadata and other
       sources 
590    Electronic reproduction. Ann Arbor, Michigan : ProQuest 
       Ebook Central, 2020. Available via World Wide Web. Access 
       may be limited to ProQuest Ebook Central affiliated 
       libraries 
650  0 Chromatographic analysis.;Clinical trials -- Statistical 
       methods.;Drug development -- Statistical 
       methods.;Pharmaceutical biotechnology 
655  4 Electronic books 
700 1  Valko, Klara 
776 08 |iPrint version:|aValko, Klara|tPhysicochemical and 
       Biomimetic Properties in Drug Discovery : Chromatographic 
       Techniques for Lead Optimization|dSomerset : John Wiley & 
       Sons, Incorporated,c2014|z9781118152126 
856 40 |uhttps://ebookcentral.proquest.com/lib/sinciatw/
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