Drug Metabolism Handbook (eBook)

Ala F. Nassar, PhD, provides technical and operational leadership in characterizing in vitro and in vivo metabolites. His research focuses on understanding how structure modification can improve the ADME profile for new chemical entities as they advance towards clinical candidacy. Recently, he identified and patented pharmacologically active metabolites of Nexavar®. Dr. Nassar serves on the Editorial Board of Drug Metabolism Letters and The Open Drug Metabolism Journal and is also a reviewer for several other journals. Paul F. Hollenberg, PhD, is Maurice H. Seevers Collegiate Professor and Chair of Pharmacologyat The University of Michigan. His current research focuses on the relationship between thestructures of the active sites of cytochrome P450s and their catalytic function. Dr. Hollenbergwas cofounder and Associate Editor of Chemical Research in Toxicology and has served onnumerous editorial boards and review panels. Joann Scatina, PhD, has over twenty-four years of drug metabolism experience, and is currentlyVice President of the Drug Metabolism Division, Drug Safety and Metabolism, for WyethResearch. Dr. Scatina's research interests include identification of metabolites, metabolicpathways and enzymes responsible, in vitro-in vivo extrapolation, and prediction of druginteractions. She is a member of the American Society for Pharmacology and ExperimentalTherapeutics and the International Society for the Study of Xenobiotics (ISSX) and is currentlyserving on the Editorial Board of Drug Metabolism Reviews.

Preface.

List of Contributors.

Part I: Introduction.

1. Historical Perspective (Roberta S. King).

2. Factors Affecting Metabolism (Roberta S. King).

3. Biotransformation sin Drug Metabolism (Roberta S. King).

4.In Vivo Metabolite Kinetics (Zheng Yang).

5. Pharmacogenetics and Pharmacogenomics (Lilian G. Yengi).

6. Introduction to drug transporters (Louis Leung and Aram
Oganesian).

Part II: Technologies for In Vitro and In Vivo
Studies.

7. Automated Drug Screening for ADMET Properties (Melvin
Reichman and Helen Gill).

8. Mass Spectrometry (Thomas R. Sharp).

9. Approaches to Performing Metabolite Elucidation: One Key to
Success in Drug Discovery and Development (Ala F. Nassar).

10. Structural Modifications of Drug Candidates: How Useful Are
They in Improving Metabolic Stability of New Drugs? Part I:
Enhancing Metabolic Stability (Ala F. Nassar).

11. Structural Modifications of Drug Candidates: How Useful Are
They in Improving PK Parameters of New Drugs? Part II: Drug Design
Strategies (Ala F. Nassar).

12. Minimizing the Potential for Drug bioactivation of drug
Candidates to Success in Clinical Development (Ala F. Nassar).

13. Screening for reactive Metabolites Using Genotoxicity Arrays
and Enzyme/DNA Biocolloids (James F. Rusling, Eli G. Hvastkovs, and
John B. Schenkman).

Part III: Drug Interactions.

14. Enzyme Inhibition (Paul F. Hellenberg).

15. Evaluating and Predicting Human Cytochrome P450 Enzyme
Induction (Michael Sinz, Sean Kim, Stephen Ferguson, and Edward
LeCluyse).

16. An Introduction to Metabolic Reaction Phenotyping (Carl D.
Davis and A. David Rodrigues).

17. Nuclear receptor-Mediated Gene Regulation in Drug Metabolism
(Hongbing Wang and Wen Xie).

18. Characterization of Cytochrome P450 Mechanism-Based
Inhibition (Dan Rock and Larry C. Wienkers).

19. Clinical Drug-Drug Interactions.

20. Pharmaceutical Excipients in drug-Drug Interaction (Chuan
Chen and Abu J. M. Sadeque).

Part IV: Toxicity.

21. The Role of Drug Metabolism in Toxicity (Carl D. Davis and
Umesh M. Hanumegowda).

22. Allergic reactions to Drugs (Mark P. Grillo).

23. Chemical Mechanism in toxicology (Mark P. Grillo).

24. Mechanisms of Reproductive Toxicity (Aileen F. Keating and
Patricia B. Hoyer).

25. An Introduction to Toxicogenomics (Aaron L. Vollrath and
Christopher A. Bradfield).

26. Role of Bioactivation Reactions in Chemically Induced
Nephrotoxicity (Lawrence H. Lash).

Part V: Regulatory Perspectives.

27. Drug Metabolism in regulatory Guidances, clinical trials,
and Product Labeling (Mark N. Milton).

Index.