Many drugs and other xenobiotics (e.g., preservatives, insecticides, and plastifiers) contain hydrolyzable moieties such as ester or amide groups. In biological media, such foreign compounds are, therefore, important substrates for hydrolytic reactions catalyzed by hydrolases or proceeding non-enzymatically. Despite their significance, until now, no book has been dedicated to hydrolysis and hydrolases in the metabolism of drugs and other xenobiotics. This work fills a gap in the literature and reviews metabolic reactions of hydrolysis and hydarion from the point of views of enzymes, substrates, and reactions.

These volumes represent a comprehensive guide to prodrugs. They guide the reader through the current status of the prodrug concept and its many applications and highlight its many successes in overcoming formulation and delivery of problematic drugs. Replete with examples of approved and marketed prodrugs, these volumes introduce the topic to the novice as well as professional in the design of prodrugs.

Part 3 of the Handbook of Experimental Pharmacology (Concepts in Biochem ical Pharmacology) applies the principles enunciated in Parts 1 and 2 to clinical pharmacology and toxicology. The major objective is to elucidate the many factors that determine the relationships between pharmacokinetic aspects of the disposition and metabolism of drugs and their therapeutic or toxic actions in man. Because of the more restricted information obtainable in human studies, this volume reflects the editors' bias that an understanding of pharmacokinetics is fundamental for assessing pharmacologic or toxicologic effects of drugs in humans. The first chapter is a unique primer on when to apply and how to use pharmaco kinetic tools in human pharmacology. The second chapter explains the general assumptions underlying pharmacokinetic approaches both in simple terms for the novice and in mathematical form for the more sophisticated reader. Several chapters on determinants of drug concentration and activity discuss drug absorption, drug latentiation, drugs acting through metabolites, entero hepatic drug circulation, influence of route of drug administration on response, genetic variations in drug disposition and response, age differences in absorption, distribution and excretion of drugs, and pathologic and physiologic factors affecting absorption, distribution and excretion of drugs and drug response. The focus of these chapters is data obtained in human, rather than animal, studies. Most of the chapters contain new material never summarized previously.

Drug Metabolism: Current Concepts provides a comprehensive understanding of the processes that take place following ingestion of a medicinal agent or xenobiotic, with an emphasis on the crucial role of metabolism (biotransformation). How a sound knowledge of these phenomena is incorporated into the design of effective new drug candidates is also explained. The user-friendly text focuses on concepts rather than extraneous details and is supported by many illustrated examples of biotransformations as well as frequent references to current critical reviews and articles highlighting the nature of research objectives in this vibrant area of medicinal development. The final topic on strategies for drug design relies on the background provided by the rest of the book. This book is ideally suited as an advanced text for courses in drug metabolism for students of medicine, pharmacy, pharmacology, biochemistry; and for courses in drug design and drug delivery for students of medicinal chemistry. It is also appropriate for professional seminars or courses that relate to the fate of a drug in the body, drug interactions, adverse reactions and drug design.

Prodrug Design: Perspectives, Approaches and Applications in Medicinal Chemistry provides a focused overview of this critical area of drug discovery, as that continuous process strives not only to discover new drug compounds but also to modify the existing ones. This valuable primer supports this mission of drug development and its goal of reducing undesired effects and improving therapeutic effectiveness of drug compounds. Providing a unique compilation of data, insightful case studies, and review of existing literature in the area, the book will promote innovation in medicinal and pharmaceutical chemistry research, exploring the limitations of existing drugs and their improvement. Prodrug Design reviews marketed compounds, the safety of promoieties, and a detailed classification of prodrugs organized by therapeutic area for easy reference. Offers unique, detailed overview of Prodrug research and literature Provides detailed chemical structures Includes Prodrug listing by therapeutic area

This topical reference and handbook addresses the chemistry, pharmacology, toxicology and the patentability of prodrugs, perfectly mirroring the integrated approach prevalent in today's drug design. It summarizes current experiences and strategies for the rational design of prodrugs, beginning at the early stages of the development process, as well as discussing organ- and site-selective prodrugs. Every company employing medicinal chemists will be interested in this practice-oriented overview of a key strategy in modern drug discovery and development.