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 organisms 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 Contents:
I. STUDIES OF MEMBRANE PERMEABILITY AND ORAL ABSORPTION Physicochemical Approaches to Drug Absorption High Throughput Measurement of log D and pKa 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

About the Author :
Han van de Waterbeemd is the editor of Drug Bioavailability: Estimation of Solubility, Permeability, Absorption and Bioavailability, published by Wiley. Hans Lennernas is the editor of Drug Bioavailability: Estimation of Solubility, Permeability, Absorption and Bioavailability, published by Wiley.

Review :
" this book would make a valuable resource for scientists working in drug discovery and early drug development (Pharmaceutical Research, June 2004) This monograph is without a doubt the most comprehensive and up to date publication on drug bioavailability available today...very highly recommended... (Journal of Medicinal Chemistry, Vol. 47, No. 7)