Drug bioavailability : estimation of solubility, permeability, absorption and bioavailability / / edited by Han van de Waterbeemd, Hans Lennernäs and Per Artursson

• Pubblicazione: Weinheim, : Wiley-VCH, c2003
• Descrizione fisica: 1 online resource (605 p.)
• Disciplina: 615.1; 615.19; 615/.7
• Soggetto topico: Drugs - Bioavailability; Drugs - Solubility
• Altri autori: WaterbeemdHan van de LennernäsHans ArturssonPer
• Note generali: Description based upon print version of record.
• Nota di bibliografia: Includes bibliographical references and index.
• Nota di contenuto: Drug 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 ; 1.9 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) ; 2.3.3.3 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 ; 3.2 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 ; 3.4.4 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 ; 3.4.11 Predictions of in vivo Human Jejunal Permeabilities using the Improved 20% Soy Lecithin with Surfactant in vitro PAMPA Technique
• Sommario/riassunto: The 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-
• Titolo autorizzato: Drug bioavailability
• ISBN: 1-280-52024-8; 9786610520244; 3-527-60515-0; 3-527-60147-3
• Formato: Materiale a stampa
• Livello bibliografico: Monografia
• Lingua di pubblicazione: Inglese
• Record Nr.: 9910877382003321
• Lo trovi qui: Univ. Federico II
• Serie: Methods and principles in medicinal chemistry ; ; v. 18.