Wiley-VCH ebook:Drug Bioavailability
Title: Drug Bioavailability: Estimation of Solubility, Permeability, Absorption and Bioavailability (Methods and Principles in Medicinal Chemistry)
Author: Han van de Waterbeemd, Raimund Mannhold, Hugo Kubinyi, Gerd Folkers, Hans Lennernas
Publisher: Wiley-VCH
Publication Date: 2003-08-08
Number Of Pages: 602
Summary:
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-called bioavailability.
Written by an international team from academia and the pharmaceutical industry, this book covers all aspects of the oral bioavailability of medicines. The focus is placed on methods for determining the parameters relevant to bioavailability. These range from modern physicochemical techniques via biological studies in vitro and in vivo right up to computer-aided predictions. The authors specifically address possibilities for optimizing bioavailability during the early screening stage for the active substance.
Its clear structure and comprehensive coverage make this book equally suitable for researchers and lecturers in industry and teaching.
Contents
I. Studies of Membrane Permeability and Oral Absorption
1. Physico-chemical Approaches to Drug Absorption
2. High-throughput Measurement of log D and pKa
3. High-throughput Measurement of Permeability Profiles
4. Caco-2 and Emerging Alternatives for Prediction of Intestinal Drug Transport: A General Overview
5. Cell Cultures in Drug Discovery: An Industrial Perspective
6. Use of Animals for the Determination of Absorption and Bioavailability
7. In Vivo Permeability Studies in the Gastrointestinal Tract of Humans
II. Drug Dissolution and Solubility
8. Gastrointestinal Dissolution and Absorption of Drugs
9. Aqueous Solubility in Discovery, Chemistry, and Assay Changes
10. Factors Influencing the Water Solubilities of Crystalline Drugs
III. Role of Transporters and Metabolism in Oral Absorption
11. Transporters in the GI Tract
12. Hepatic Transport
13. The Importance of Gut Wall Metabolism in Determining Drug Bioavailability
14. Modified Cell Lines
IV. Computational Approaches to Drug Absorption and Bioavailability
15. Intestinal Absorption: The Role of Polar Surface Area
16. Calculated Molecular Properties and Multivariate Statistical Analysis in Absorption Prediction
17. VOLSURF: A Tool for Drug ADME-properties Prediction
18. Simulation of Absorption, Metabolism, and Bioavailability
19. Prediction of Bioavailability
20. Towards P-Glycoprotein Structure-Activity Relationships
V. Drug Development Issues
21. Application of the Biopharmaceutical Classification System Now and in the Future
22. Prodrugs
23. Modern Delivery Strategies: Physiological Considerations for Orally Administered Medications
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