Author Valko, Klara
Title Physicochemical and Biomimetic Properties in Drug Discovery : Chromatographic Techniques for Lead Optimization
Imprint Somerset : John Wiley & Sons, Incorporated, 2014
©2014
book jacket
Edition 1st ed
Descript 1 online resource (453 pages)
text txt rdacontent
computer c rdamedia
online resource cr rdacarrier
Note 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
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
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
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
Description based on publisher supplied metadata and other sources
Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2020. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
Link Print version: Valko, Klara Physicochemical and Biomimetic Properties in Drug Discovery : Chromatographic Techniques for Lead Optimization Somerset : John Wiley & Sons, Incorporated,c2014 9781118152126
Subject Chromatographic analysis.;Clinical trials -- Statistical methods.;Drug development -- Statistical methods.;Pharmaceutical biotechnology
Electronic books
Alt Author Valko, Klara