Han van de Waterbeemd & Hans Lennernäs 
Drug Bioavailability 
Estimation of Solubility, Permeability, Absorption and Bioavailability

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.

Table of Content

I. STUDIES OF MEMBRANE PERMEABILITY AND ORAL ABSORPTION
Physicochemical Approaches to Drug Absorption
High Throughput Measurement of log D and p Ka
High Throughput Measurement of Membrane Permeability
Biosensors to Study Intestinal Drug Absorption
Cell Cultures of Caco-2, MDCK and Other Cell Lines: General Overview
Cell Cultures in Drug Discovery: An Industrial Perspective
Role of Animals in Absorption and Bioavailability Estimation
In Vivo Permeability Studies in the GI Tract
II. DRUG DISSOLUTION AND SOLUBILITY
Gastrointestinal Dissolution and Absorption of Drugs
Solubility Screening in Drug Discovery
Impact of Salt/Crystal Forms on Solubility and Permeability in Drug Development
Prediction of Solubility
III. ROLE OF TRANSPORTERS AND METABOLISM IN ORAL ABSORPTION
Transporters in the GI Tract
Role of Transporters in Liver Extraction of Drugs
Gut Wall Metabolism
Modified Cell Lines
IV. COMPUTATIONAL APPROACHES TO DRUG ABSORPTION AND BIOAVAILABILITY
Intestinal Absorption: The Role of Polar Surface Area
Calculated Molecular Properties and Multivariate Statistical Analysis in Absorption Prediction
2D and 3D Molecular Descriptors in ADME prediction
Simulation of the Absorption Process
Prediction of Bioavailability
Towards P-gp Structure-Activity Relationships
V. DRUG DEVELOPMENT ISSUES
Biopharmaceutical Classification System: How Important Are Solubility and Permeability?
Prodrugs