Drug Bioavailability

Han van de Waterbeemd studied physical organic chemistry at the Technical University of Eindhoven, and gained his PhD in medicinal chemistry from the University of Leiden. After an academic career at the University of Lausanne with Bernard Testa, he worked for 20 years in the pharmaceutical industry for Roche, Pfizer and AstraZeneca. His research interests are in optimizing compound quality using measured and predicted physicochemical and DMPK properties. He has contributed to 145 research papers and book chapters, and (co-)edited 13 books, and was involved in organizing conferences and courses to promote medicinal chemistry, with a focus on physicochemistry and predictive approaches in drug design. Dr. van de Waterbeemd is on the editorial board of several journals and of Methods and Principles in Medicinal Chemistry.
 
Bernard Testa is Emeritus Professor of the University of Lausanne, having served there for 25 years as a full professor and head of medicinal chemistry. He has written 5 books and edited 33 others, and (co)-authored well over 450 research and review articles in the fields of drug design and drug metabolism. Between 1994 and 1998, he was the European Editor of Pharmaceutical Research, and is now a senior editor of Chemistry and Biodiversity, as well as serving on the editorial boards of several leading journals. Professor Testa holds honorary doctorates from the universities of Milan, Montpellier and Parma, and is a recipient of the Nauta Award on Pharmacochemistry given by the European Federation for Medicinal Chemistry.

21 Kapitel, durchgesehen und aktualisiert: In diesem neu aufgelegten Standardwerk erklären Wirkstoffforscher aus dem akademischen und industriellen Umfeld alle Faktoren, die die Bioverfügbarkeit von Wirkstoffen beeinflussen. Teil 1 konzentriert sich auf die Messung physikalischer Eigenschaften (in vivo und in vitro), Teil 2 diskutiert Löslichkeit und gastrointestinale Absorption, Teil 3 widmet sich Fragen des Metabolismus und der Exkretion. Der besonders intensiv überarbeitete Teil 4 geht auf moderne Computermodelle zur Abschätzung der Bioverfügbarkeit potenzieller Wirksubstanzen ein. Der letzte Teil beschäftigt sich mit der Verbesserung der Bioverfügbarkeit durch maßgeschneiderte Syntheseprozesse. -- Mit Beiträgen von Wissenschaftlern führender Pharmaunternehmen wie Pfizer, AstraZeneca und Roche!

The 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.

Introduction
 
Part I. Physicochemical Aspects of Drug Dissolution and Solubility
 
Aqueous Solubility in Discovery Chemistry, DMPK and Biological Assays
Gastrointestinal Dissolution and Absorption of Class II Drugs
In Silico Prediction of Aqueous Solubility
 
Part II. Physicochemical and Biological Studies of Membrane Permeability and Oral Absorption
 
Physico-chemical Approaches to Drug Absorption
High-throughput Measurement of Physicochemical Properties (pKa, solubility, log D, permeability)
Cell Cultures for Permeability Assessment in Drug Discovery
Use of Animals for the Determination of Absorption and Bioavailability
In vivo Permeability Studies in the GI Tract of Humans
 
Part III Role of Transporters and Metabolism in Oral Absorption
 
Transporters in the GI Tract
Hepatic Drug Transport
The Importance of Gut Wall Metabolism in Determining Drug Bioavailability
Modified Cell Lines to Assess Active Transport and Metabolism during Absorption
 
Part IV Computational Approaches to Drug Absorption and Bioavailability
 
Calculated Molecular Properties and Multivariate Statistical Analysis
Computational Absorption Prediction
In Silico Prediction of Bioavailability
Simulation of Absorption, Metabolism, and Bioavailability
P-Glycoprotein Structure-Activity Relationships
 
Part V Drug Development Issues
 
Application of the Biopharmaceutical Classification System Now and in the Future
Prodrugs
Modern Delivery Strategies: Physiological Considerations for Orally Administered Medications
The Promise of Nanotechnology in Drug Delivery