Hydrolysis In Drug And Prodrug Metabolism

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.

Standard medicinal chemistry courses and texts are organized by classes of drugs with an emphasis on descriptions of their biological and pharmacological effects. This book represents a new approach based on physical organic chemical principles and reaction mechanisms that allow the reader to extrapolate to many related classes of drug molecules. The Second Edition reflects the significant changes in the drug industry over the past decade, and includes chapter problems and other elements that make the book more useful for course instruction. New edition includes new chapter problems and exercises to help students learn, plus extensive references and illustrations Clearly presents an organic chemist's perspective of how drugs are designed and function, incorporating the extensive changes in the drug industry over the past ten years Well-respected author has published over 200 articles, earned 21 patents, and invented a drug that is under consideration for commercialization

The prodrug approach is a promising and well established strategy for the development of new entities that possess superior efficacy, selectivity and reduced toxicity. Hence an optimised therapeutic outcome can be accomplished using this approach. Prodrug design is becoming more elaborate in the development of efficient and selective drug delivery systems. The targeted prodrug approach, in combination with gene delivery and controlled expression of enzymes and carrier proteins, is a promising strategy for precise and efficient drug delivery and enhancement of the therapeutic effect. This book describes in details all prodrug approaches and examples of prodrugs that succeeded to enter the market. There are two major prodrug design approaches that are considered as widely used among all other approaches: the targeted drug design approach by which prodrugs can be designed to target specific enzymes or carriers by considering enzyme-substrate specificity or carrier-substrate specificity in order to overcome various undesirable drug properties. Examples for such approach is the antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT), virus-directed enzyme prodrug therapy (VDEPT) and GDEPT. In addition, this book describes in details a novel prodrug chemical approach which is based on intramolecular reactions that were utilised to understand how enzymes exert their high catalysis. The information gained from the experimental and theoretical calculations on these enzyme models was used to design efficient chemical moieties to be utilised as prodrug linkers with the potential to release the corresponding parent drugs in a slow or fast release manner. Several prodrugs for commonly used drugs suffer from low bioavailability or/and bitter sensation were designed using quantum mechanics methods (DFT and ab initio) and recently a large number among these prodrugs were synthesised. Examples of such prodrugs are presented in the different chapters of the book.

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

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.