Drug development absorption

Avdeef, A. Absorption and Drug Development, Wiley-Interscience, Hoboken, N), 2003. 

An analysis of the solubility and absorption rates for the 254 drugs considered here shows that the 25 compounds fulfilling the condition of 0.25a - XQ > 5.0 and HQi > 20.0 have solubility of only a few micrograms per milHHter, and are absorbed at the level of only a few percents. Such properties are too poor for drug development, so these parameters can be useful as an alert in computer-aided compound selection. 

Preclinical drug development also involves animal testing [61]. Data from one rodent species and one nonrodent species are usually collected to determine the absorption, metabolism, and toxicity characteristics of the compound. Both short-term (2 weeks to 3 months) and long-term (up to several years) studies are done. The long-term studies are particularly useful for... 

Absorption and Drug Development Solubility, Permeability, and Charge State. By Alex Avdeef ISBN 0-471-423653. Copyright 2003 John Wiley Sons, Inc. 

Absorption and drug development solubility, permeability, and charge state / Alex Avdeef. p. cm. 

This book is written for the practicing pharmaceutical scientist involved in absorption-distribution-metabolism-excretion (ADME) measurements who needs to communicate with medicinal chemists persuasively, so that newly synthesized molecules will be more drug-like. ADME is all about a day in the life of a drug molecule (absorption, distribution, metabolism, and excretion). Specifically, this book attempts to describe the state of the art in measurement of ionization constants (p Ka), oil-water partition coefficients (log PI log D), solubility, and permeability (artificial phospholipid membrane barriers). Permeability is covered in considerable detail, based on a newly developed methodology known as parallel artificial membrane permeability assay (PAMPA). 

This volume gives an overview of the current status and an outlook to future more reliable predictive approaches. It is subdivided in five sections dealing with studies of membrane permeability and oral absorption, drug dissolution and solubility, the role of transporters and metabolism in oral absorption, computational approaches to drug absorption and bioavailability, and finally with certain drug development issues. 

The volume is divided into five sections. Part one looks at the experimental study of membrane permeability and oral absorption. In Part two, problems of measuring and prediction solubility, as one of the key determinants in the absorption process, will be discussed in detail. In the next part, progress in the science around transporter proteins and gut wall metabolism and their effect on the overall absorption process is presented. Part four looks at the in silico approaches and models to predict permeability, absorption and bioavailability. In the last part of the book, a number of drug development issues will be highlighted, which could have an important impact of the overall delivery strategies for oral pharmaceutical products. 

The termination of fialuridine and torcetrapib can be considered as worst case scenarios in drug development. In over 50% of all cases, project termination occurs due to less spectacular reasons such as a lack of efficacy or liberation-absorption-distribution-metabolism-excretion (LADME) problems (Figure 1.4) [65]. 

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