In order to avoid late-stage drug failure due to factors such as undesirable metabolic instability, toxic metabolites, drug-drug interactions, and polymorphic metabolism, an enormous amount of effort has been expended by both the pharmaceutical industry and academia towards developing more powerful techniques and screening assays to identify the metabolic profiles and enzymes involved in drug metabolism. This book presents some in-depth reviews of selected topics in drug metabolism. Among the key topics covered are: the interplay between drug transport and metabolism in oral bioavailability; the influence of genetic and epigenetic factors on drug metabolism; impact of disease on transport and metabolism; and the use of novel microdosing techniques and novel LC/MS and genomic technologies to predict the metabolic parameters and profiles of potential new drug candidates.

This book continues to be the definitive reference on drug metabolism with an emphasis on new scientific and regulatory developments. It has been updated based on developments that have occurred in the last 5 years, with new chapters on large molecules disposition, stereo-selectivity in drug metabolism, drug transporters and metabolic activation of drugs. Some chapters have been prepared by new authors who have emerged as subject area experts in the decade that has passed since publication of the first edition.

A valuable reference tool for professionals involved in the industry, Drug Metabolism in Pharmaceuticals covers new tools such as LC-MS and LC-MS-NMR along with experimental aspects of drug metabolism. This work fills a gap in the literature by covering the concepts and applications of pharmaceutical research, development, and assessment from the point of view of drug metabolism. By providing both a solid conceptual understanding of the drug metabolism system, and a well illustrated, detailed demonstration and explanation of cutting edge tools and techniques, this book serves as a valuable reference tool for bench scientists, medical students, and students of general health sciences.

Mass spectrometry (MS) is fast becoming the premier tool for analyzing various drug metabolism samples in the early phases of drug discovery and research. Introducing the newer, more powerful MS equipment and exploring new applications for using them, this book provides a state-of-the-art look at this promising field. Using Mass Spectrometry

This timely reference discusses mass spectrometry in drug metabolism and pharmacokinetic studies. With contributions by professionals from the pharmaceutical industry, this book begins with a review of current mass spectrometry techniques and applications, followed by discussions of various methods for using MS in drug metabolism studies and pharmacokinetics. Highlighting the critical importance of ADME studies for understanding how a drug is absorbed, distributed, metabolized, and excreted by the body, the book s focuses on the use of LC/MS and MALDI-MS. This is a valuable reference for scientists in the pharmaceutical industry, medicine, academia, and even those working in homeland defense.

This introduction to the mechanisms by which the body metabolizes and excretes administered drugs is directed at advanced undergraduate biochemists, pharmacologists, pre-clinical medical students and advanced undergraduate/postgraduate toxicologists.

This book, Drug Metabolism and Pharmacokinetics, delivers the latest information on biotransformation and other pharmacokinetic parameters required to assess drug safety in drug discovery and development. Drug metabolism and pharmacokinetics (DMPK) is considered a rational strategy for the design, optimization, and selection of successful drug candidates in the pre-clinical stages of drug discovery. The evaluation of various pharmacokinetic parameters such as aqueous solubility, lipophilicity, cell permeability, bioavailability, protein binding, and metabolism and elimination half-life, drug–drug interactions (DDIs), and toxicokinetics is essential for a candidate drug to become a successful therapeutic agent. This book discusses recent advances in in-silico tools and in vitro/in vivo experimental techniques applied in pharmacokinetic, metabolomic, and bioanalytical studies. Key Features: • Presents pharmacokinetic and biotransformation parameters used for pre-clinical safety evaluations • Depicts experimental and biophysical techniques used in bioanalytical and metabolomic studies • Summarizes in silico, in vitro, and in vivo methods used in drug–enzyme interactions, drug– drug interactions, and toxicokinetics Written by a global team of experts, this book is a valuable resource for drug discovery scientists, drug developers, medicinal chemists, pharmacologists, biochemists, clinicians, biomedical scientists, healthcare professionals, researchers, teaching faculty, and students.

Reports in the popular press about the increasing longevity of Americans and the aging of the baby boom generation are constant reminders that the American population is becoming older. Consequently, an issue of growing medical, health policy, and social concern is the appropriate and rational use of medications by the elderly. Although becoming older does not necessarily correlate with increasing illness, aging is associated with anatomical and physiological changes that affect how medications are metabolized by the body. Furthermore, aging is often related to an increased frequency of chronic illness (often combined with multiple health problems) and an increased use of medications. Thus, a better understanding of the absorption, distribution, metabolism, and excretion of drugs; of the physiologic responses to those medications; as well as of the interactions among multiple medications is crucial for improving the health of older people.

In the pharmaceutical industry, the incorporation of the disciplines of pharma- kinetics, pharmacodynamics, and drug metabolism (PK/PD/DM) into various drug development processes has been recognized to be extremely important for approp- ate compound selection and optimization. During discovery phases, the identifi- tion of the critical PK/PD/DM issues of new compounds plays an essential role in understanding their pharmacological profiles and structure-activity relationships. Owing to recent progress in analytical chemistry, a large number of compounds can be screened for their PK/PD/DM properties within a relatively short period of time. During development phases as well, the toxicology and clinical study designs and trials of a compound should be based on a thorough understanding of its PK/PD/DM properties. During my time as an industrial scientist, I realized that a reference work designed for practical industrial applications of PK/PD/DM could be a very valuable tool for researchers not only in the pharmacokinetics and drug metabolism departments, but also for other discovery and development groups in pharmaceutical companies. This book is designed specifically for industrial scientists, laboratory assistants, and managers who are involved in PK/PD/DM-related areas. It consists of thirteen chapters, each of which deals with a particular PK/PD/DM issue and its industrial applications. Chapters 3 and 12 in particular address recent topics on higher throughput in vivo exposure screening and the prediction of pharmacokinetics in humans, respectively. Chapter 8 covers essential information on drug metabolism for industrial scientists.

The first professional reference on this highly relevant topic, for drug developers, pharmacologists and toxicologists. The authors provide more than a systematic overview of computational tools and knowledge bases for drug metabolism research and their underlying principles. They aim to convey their expert knowledge distilled from many years of experience in the field. In addition to the fundamentals, computational approaches and their applications, this volume provides expert accounts of the latest experimental methods for investigating drug metabolism in four dedicated chapters. The authors discuss the most important caveats and common errors to consider when working with experimental data. Collating the knowledge gained over the past decade, this practice-oriented guide presents methods not only used in drug development, but also in the development and toxicological assessment of cosmetics, functional foods, agrochemicals, and additives for consumer goods, making it an invaluable reference in a variety of disciplines.