Ronald Borchardt - Böcker

Drug discovery and development is a very complex, costly, and ti- consuming process. Because of the uncertainties associated with predicting the pharmacological effects and the toxicity characteristics of new chemical entities in man, their clinical development is quite prone to failure. In recent years, phar- ceutical companies have come under increasing pressure to introduce new blockbuster drugs into the marketplace more rapidly. Companies have responded to these pressures by introducing new technologies and new strategies to expedite drug discovery and development. Drug discovery and development have traditionally been divided into three separate processes (i. e. , discovery research, preclinical development, and clinical development) that ideally should be integrated both organizationally and functionally. Instead, separate and distinct discovery research, preclinical development, and clinical development divisions were created within many companies during the 1980s and 1990s, Because of their isolation, scientists in the discovery research divisions often were advancing drug candidates into preclinical development that had marginal drug-like properties. For the purpose of this presentation, “drug-like” properties refer to the molecule’s physicochemical, absorption-distribution-metabolism-excretion (ADME), and toxicological properties. Lacking optimal drug-like properties often caused these drug candidates to fail in preclinical or clinical development.

Prodrugs are substances administered in an inactive form that is then metabolized in the body in vivo into the active compound. The rationale behind administering prodrugs is to optimize absorption, distribution, metabolism, and excretion of these drugs. Since first described in the 1950s, prodrugs continue to be a fertile area of research. There are a number of small pharmaceutical/biotech companies dedicated to using prodrugs for the delivery of older but problematic drugs as well as to developing broad-based prodrug technologies for application to new and future drugs. These volumes represent a comprehensive guide to prodrugs and will guide the reader through the current status of the prodrug concept and its many applications and to highlight its many successes in overcoming formulation and delivery of problematic drugs.

At a time when pharmaceutical companies have limited resources to develop newer and better drugs, they must continually evaluate the effectiveness and efficiency of their research and development process. This volume focuses on how to increase the efficiency of drug discovery and development. Written by experienced discovery scientists from diverse disciplines, including chemistry, drug metabolism, and development sciences, it details in silico, in vitro, and in vivo tools for prediction, measurement, and application of compound properties to select and improve potential drug candidates.

Drug discovery and development is a very complex, costly, and ti- consuming process. Because of the uncertainties associated with predicting the pharmacological effects and the toxicity characteristics of new chemical entities in man, their clinical development is quite prone to failure. In recent years, phar- ceutical companies have come under increasing pressure to introduce new blockbuster drugs into the marketplace more rapidly. Companies have responded to these pressures by introducing new technologies and new strategies to expedite drug discovery and development. Drug discovery and development have traditionally been divided into three separate processes (i. e. , discovery research, preclinical development, and clinical development) that ideally should be integrated both organizationally and functionally. Instead, separate and distinct discovery research, preclinical development, and clinical development divisions were created within many companies during the 1980s and 1990s, Because of their isolation, scientists in the discovery research divisions often were advancing drug candidates into preclinical development that had marginal drug-like properties. For the purpose of this presentation, “drug-like” properties refer to the molecule’s physicochemical, absorption-distribution-metabolism-excretion (ADME), and toxicological properties. Lacking optimal drug-like properties often caused these drug candidates to fail in preclinical or clinical development.