LEADER 05455nam 2200673Ia 450 001 9910830618603321 005 20220311124652.0 010 $a1-282-30704-5 010 $a9786612307041 010 $a3-527-62386-8 010 $a3-527-62387-6 035 $a(CKB)1000000000799524 035 $a(EBL)481429 035 $a(SSID)ssj0000294343 035 $a(PQKBManifestationID)11195940 035 $a(PQKBTitleCode)TC0000294343 035 $a(PQKBWorkID)10322607 035 $a(PQKB)10519302 035 $a(MiAaPQ)EBC481429 035 $a(OCoLC)476317498 035 $a(PPN)243292252 035 $a(EXLCZ)991000000000799524 100 $a20080616d2009 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 00$aDrug bioavailability$b[electronic resource] $eestimation of solubility, permeability, absorption and bioavailability 205 $a2nd, completely rev. ed /$bedited by Han van de Waterbeemd and Bernard Testa. 210 $aWeinheim $cWiley-VCH$dc2009 215 $a1 online resource (653 p.) 225 1 $aMethods and principles in medicinal chemistry ;$v40 300 $aDescription based upon print version of record. 311 $a3-527-32051-2 320 $aIncludes bibliographical references and index. 327 $aDrug Bioavailability: Estimation of Solubility, Permeability, Absorption and Bioavailability; Contents; List of Contributors; Preface; A Personal Foreword; 1 Introduction: The Why and How of Drug Bioavailability Research; 1.1 Dening Bioavailability; 1.1.1 The Biological Context; 1.1.2 A Pharmacokinetic Overview; 1.1.3 Specic Issues; 1.2 Presentation and Layout of the Book; References; Part One Physicochemical Aspects of Drug Dissolution and Solubility; 2 Aqueous Solubility in Drug Discovery Chemistry, DMPK, and Biological Assays; 2.1 Introduction; 2.1.1 Denition of Aqueous Solubility 327 $a2.1.2 Aqueous Solubility in Different Phases of Drug Discovery2.2 Aqueous Solubility in Hit Identication; 2.2.1 Aqueous Solubility from DMSO Solutions; 2.2.1.1 Turbidimetric Methods; 2.2.1.2 UV Absorption Methods; 2.2.1.3 Alternative Detection Methodology; 2.2.1.4 Application of DMSO-Based Solubility Assays; 2.3 Aqueous Solubility in Lead Identication and Lead Optimization; 2.3.1 Dried-Down Solution Methods; 2.3.2 Solubility from Solid; 2.3.3 Thermodynamic Solubility Assays with Solid-State Characterization; 2.3.4 Solubility by Potentiometry 327 $a2.3.5 Application of Thermodynamic Solubility Data in LI and LO2.4 Conclusions; References; 3 Gastrointestinal Dissolution and Absorption of Class II Drugs; 3.1 Introduction; 3.2 Drug Absorption and the BCS; 3.3 Class II Drugs; 3.4 GI Physiological Variables Affecting Class II Drug Dissolution; 3.4.1 Bile Salts; 3.4.2 GI pH; 3.4.3 GI Transit; 3.4.4 Drug Particle Size; 3.4.5 Volume Available for Dissolution; 3.5 In Vitro Dissolution Tests for Class II Drugs; 3.5.1 Biorelevant Media; 3.5.2 Dynamic Lipolysis Model; 3.6 BCS-Based FDA Guidelines: Implications for Class II Drugs 327 $a3.6.1 Potential of Redening BCS Solubility Class Boundary3.6.2 Biowaiver Extension Potential for Class II Drugs; 3.7 Conclusions; References; 4 In Silico Prediction of Solubility; 4.1 Introduction; 4.2 What Solubility Measures to Model?; 4.3 Is the Data Set Suitable for Modeling?; 4.4 Descriptors and Modeling Methods for Developing Solubility Models; 4.5 Comparing Literature Solubility Models; 4.6 What Is the Inuence of the Domain of Applicability?; 4.7 Can We Tell when Good Predictions Are Made?; 4.8 Conclusions; References 327 $aPart Two Physicochemical and Biological Studies of Membrane Permeability and Oral Absorption5 Physicochemical Approaches to Drug Absorption; 5.1 Introduction; 5.2 Physicochemical Properties and Pharmacokinetics; 5.2.1 DMPK; 5.2.2 Lipophilicity, Permeability, and Absorption; 5.2.3 Estimation of Volume of Distribution from Physical Chemistry; 5.2.4 Plasma Protein Binding and Physicochemical Properties; 5.3 Dissolution and Solubility; 5.3.1 Calculated Solubility; 5.4 Ionization (pKa); 5.4.1 Calculated pKa; 5.5 Molecular Size and Shape; 5.5.1 Calculated Size Descriptors; 5.6 Hydrogen Bonding 327 $a5.6.1 Calculated Hydrogen-Bonding Descriptors 330 $aThe gold standard for industrial research now completely revised in line with current trends in the field, with all contributions extensively updated or rewritten. In 21 chapters readers can benefit from the key working knowledge of today's leading pharmaceutical companies, including Pfizer, AstraZeneca, and Roche. Drug developers from industry and academia present all the factors governing drug bioavailability, complete with practical examples and real-life data. Part I focuses on in vitro and in vivo measurements of physicochemical properties, such as membrane permeability and ioniza 410 0$aMethods and principles in medicinal chemistry ;$v40. 606 $aDrugs$xBioavailability 606 $aPharmaceutical chemistry 615 0$aDrugs$xBioavailability. 615 0$aPharmaceutical chemistry. 676 $a615.19 676 $a664.06 701 $aWaterbeemd$b Han van de$0860600 701 $aTesta$b Bernard$0290760 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910830618603321 996 $aDrug bioavailability$94107077 997 $aUNINA