LEADER 05395nam 2200673Ia 450 001 9910877382003321 005 20230617021407.0 010 $a1-280-52024-8 010 $a9786610520244 010 $a3-527-60515-0 010 $a3-527-60147-3 035 $a(CKB)1000000000019314 035 $a(EBL)481275 035 $a(SSID)ssj0000141534 035 $a(PQKBManifestationID)11147200 035 $a(PQKBTitleCode)TC0000141534 035 $a(PQKBWorkID)10090060 035 $a(PQKB)11289588 035 $a(MiAaPQ)EBC481275 035 $a(OCoLC)55689617 035 $a(EXLCZ)991000000000019314 100 $a20021028d2003 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 00$aDrug bioavailability $eestimation of solubility, permeability, absorption and bioavailability /$fedited by Han van de Waterbeemd, Hans Lennerna?s and Per Artursson 210 $aWeinheim $cWiley-VCH$dc2003 215 $a1 online resource (605 p.) 225 1 $aMethods and principles in medicinal chemistry ;$vv. 18 300 $aDescription based upon print version of record. 311 $a3-527-30438-X 320 $aIncludes bibliographical references and index. 327 $aDrug Bioavailability Estimation of Solubility, Permeability, Absorption and Bioavailability; Contents; Preface; Foreword; List of Authors; I Studies of Membrane Permeability and Oral Absorption; 1 Physico-chemical Approaches to Drug Absorption; Abbreviations; Symbols; 1.1 Introduction; 1.2 Drug-like Properties; 1.3 Dissolution and Solubility; 1.3.1 Calculated Solubility; 1.4 Ionization (pK(a)); 1.5 Lipophilicity; 1.5.1 Calculated log P; 1.6 Molecular Size and Shape; 1.6.1 Calculated Size Descriptors; 1.7 Hydrogen Bonding; 1.7.1 Calculated Hydrogen-Bonding Descriptors; 1.8 Amphiphilicity 327 $a1.9 Permeability1.9.1 Artificial Membranes; 1.9.2 IAM, ILC, MEKC, and BMC; 1.9.3 Liposome Partitioning; 1.9.4 Biosensors; 1.9.5 Ghost Erythrocytes and Diffusion Constants; References; 2 High-throughput Measurement of log D and pK(a); Abbreviations; Symbols; 2.1 Introduction; 2.2 Relationship between Ionization and Lipophilicity; 2.3 Measuring log D; 2.3.1 Shake-flask Method; 2.3.2 pH-metric Method; 2.3.3 Direct Chromatographic Methods; 2.3.3.1 Chromatographic Hydrophobicity Index (CHI); 2.3.3.2 Microemulsion Electrokinetic Chromatography (MEEKC) 327 $a2.3.3.3 Chromatography in the Presence of Octanol2.3.3.4 Reversed-Phase Chromatography; 2.3.3.5 Liquid-Liquid Partition Chromatography; 2.4 Measuring pK(a); 2.4.1 Review of Methods; 2.4.2 The Effect of Co-solvents on pK(a); 2.4.3 pH-Metric Titration; 2.4.4 Hybrid pH-Metric/UV Method; 2.4.5 Other Methods; 2.4.6 pH Gradient Titration; 2.5 Some Thoughts about High-throughput Analytical Chemistry; Acknowledgments; References; 3 High-throughput Measurement of Permeability Profiles; Abbreviations; Symbols; 3.1 Introduction 327 $a3.2 Key Historical Developments in Artificial-Membrane Permeability Measurement3.3 The Ideal in vitro Artificial Membrane Permeability Model; 3.3.1 Lipid Compositions in Biological Membranes; 3.3.2 Permeability-pH Considerations; 3.3.3 Role of Serum Proteins; 3.3.4 Effects of Cosolvents, Bile Acids, and other Surfactants; 3.3.5 Components of the Ideal; 3.4 New Directions in PAMPA; 3.4.1 Concentrated and Charged Phospholipid Membranes; 3.4.2 Gradient-pH Permeability Equation; 3.4.3 Permeability Measurements: High-phospholipid in Surfactant-free Solutions 327 $a3.4.4 Membrane Retention Measurements: High-phospholipid in Surfactant-free Solutions3.4.5 Egg Lecithin and the Degree of Negative Charge; 3.4.6 Summary: Increasing Phospholipid Content in the Absence of Sink Conditions; 3.4.7 Effects of Surfactant on High-phospholipid Membrane Permeability and Retention; 3.4.8 Quality and Usefulness of the UV Spectra; 3.4.9 Iso-pH and Gradient-pH Mapping in 2% DOPC-Dodecane; 3.4.10 Iso-pH Mapping in 20% Soy Lecithin-Dodecane, with Surfactant 327 $a3.4.11 Predictions of in vivo Human Jejunal Permeabilities using the Improved 20% Soy Lecithin with Surfactant in vitro PAMPA Technique 330 $aThe peroral application (swallowing) of a medicine means that the body must first resorb the active substance before it can begin to take effect. The efficacy of drug uptake depends on the one hand on the chemical characteristics of the active substance, above all on its solubility and membrane permeability. On the other hand, it is determined by the organism's ability to absorb pharmaceuticals by way of specific transport proteins or to excrete them. Since many pharmacologically active substances are poorly suited for oral intake, a decisive criterion for the efficacy of a medicine is its so- 410 0$aMethods and principles in medicinal chemistry ;$vv. 18. 606 $aDrugs$xBioavailability 606 $aDrugs$xSolubility 615 0$aDrugs$xBioavailability. 615 0$aDrugs$xSolubility. 676 $a615.1 676 $a615.19 676 $a615/.7 701 $aWaterbeemd$b Han van de$0860600 701 $aLennerna?s$b Hans$01763943 701 $aArtursson$b Per$01763944 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910877382003321 996 $aDrug bioavailability$94204632 997 $aUNINA