Metabolite Safety in Drug Development

Metabolism is the primary method to clear a drug from the body, but the normal process can generate metabolites that have intrinsic chemical reactivity towards cellular molecules and these metabolites remain free to circulate and exert both pharmacological and toxicological effects. Therefore, the study of drug metabolism occurs at all stages in the drug discovery and drug development process.

Targeting practitioners in all areas of nonclinical toxicology and clinical development, Metabolite Safety in Drug Development focuses on the characterization of metabolites once a drug candidate is selected, featuring case studies to illustrate lessons learned and a perspective on future directions. The book reviews the analytical techniques and experimental designs critical for metabolite studies, emphasizing stable and circulating metabolites and deals with (on and off) target pharmacology, in vitro systems aligned to toxicity tests, and drug–drug interactions.

Deigned to provide a comprehensive resource that offers clear guidance on one of the most critical issues of drug development, this book has a number of key benefits that include:

          Description of analytical methods like chirality, species differences, mass spectrometry, radiolabels, and in vitro / in vivo correlation
          Presentation and assessment of regulatory requirements from the US FDA and EMA
          Perspectives from authors with firsthand involvement in industry and the study of drug metabolites, including viewpoints that have influenced regulatory guidelines

Suzanne Iverson, PhD, is Head of Operations of the Department of Medical Physics and Technology at Sahlgrenska University Hospital. Previously, she was Senior Regulatory Toxicologist at AstraZeneca and has over 13 years experience in the pharmaceutical industry. Since 2011, she has served on the management committee of the European Drug Metabolism Discussion Group and the Board of the PK–Metabolism sub–committee of the Swedish Pharmaceutical Society.

Dennis Smith, PhD, currently holds part–time advisory and academic positions and, previously, worked in the pharmaceutical industry for 32 years. He has co–authored over 150 publications; and his books include 3 editions of the book Pharmacokinetics and Metabolism in Drug Design and Reactive Drug Metabolites, which are published by Wiley.