Hydrolysis in Drug and Prodrug Metabolism
Back Home Up Next

 

Bernard Testa, Joachim M. Mayer

Hydrolysis in Drug and Prodrug Metabolism: Chemistry, Biochemistry, and Enzymology

 

 

 

 




ISBN: 3-906390-25-X
Hardcover
800 pages
August 2003

Description

Xenobiotic metabolism is a subject of broad interdisciplinary, encompassing physiology, pathophysiology, pharmacology, toxicology, environmental issues, biochemistry, genetics, medical chemistry, computational (bio)chemistry, analytical chemistry, etc., and reactions of hydrolysis play a central role in metabolic pathways. Benard Testa is very well-known for his capacity to conceptualize reactions of drug metabolism, and, in this volume, he presents a comprehensive review of all metabolic reactions and enzymes involved in the hydrolysis of drugs and prodrugs. Nothing of this sort has been written before, as hydrolysis together with some other reactions of drug metabolism have long been in the shadow of the drug-metabolism community’s preoccupation with the ‘P450 hype’ and the superfamily of CYP genes coding for oxidative enzymes of drug metabolism. Recent developments, such as peptide drugs or inhibitors of cholinesterases, have lent new importance to these ‘other’ important enzymes of drug metabolism. Bernard Testa’s fundamental knowledge of this field and his commitment to clear conceptualization and precise language make this book, sadly delayed by the untimely death of Joachim Mayer, another important addition to his contributions that help us to understand the principles of xenobiotic biotransformation.

Index

  1. Introduction: Metabolic Hydrolysis and Prodrug Design.

  2. Classification, Localization, and Some Physiological Roles of Hydrolytic Enzymes.

  3. Catalytic Mechanisms of  Hydrolytic Enzymes.

  4. The Hydrolysis of Amides.

  5. The Hydrolysis of Lactams.

  6. The Hydrolysis of Peptides.

  7. The Hydrolysis of Carboxylic Acid Esters.

  8. The Hydrolysis of Carboxylic Acid Ester Prodrugs.

  9. The Cleavage of Esters of Inorganic Acids.

  10. The Hydration of Epoxides.

  11. Miscellaneous Reactions of Hydration and Dehydration.

  12. Conclusion: The Biochemistry of Water.

  13. Index.

Reviews

"In summary, this book succeeds on many levels.  At once it provides a clear and well-organized introduction to hydrolysis reactions in drug metabolism and drug design, a compendium of reaction mechanisms with extensive examples, and a comprehensive and eloquent treatise on the similarities, differences, and unifying principles of these reactions in metabolism.” (Journal of Medicinal Chemistry, 2004 Vol. 47 No. 10)

 

"As Professor Mayer states in the forward, "Nothing of this sort has been written before, as hydrolysis together with some other reactions of drug metabolism have long been in the shadow of the ‘P450 hype’." But bluntly, Bernard Testa and Joachim Mayer have identified a gaping void in the literature and written a thorough and comprehensive review to fill it.

Physically, the book is beautifully presented on high quality paper and one aspect that I particularly like is the plethora of illustrations. As well as the aforementioned reaction schemes, the structure of every compound (and in some chapters this is over two hundred) is drawn out. The bibliography is meticulous with nearly 2000 articles cited at the end of the chapters. Apart from acting as a valuable reference work for the specialists, this book would make a useful addition to any academic library, the only drawback being that it would make writing essays on the subject far too easy."

Robert Harris, School of Biosciences, University Birmingham (ISSX Newsletter, Winter 2004, Vol. 24, Issue Number 4, page 30).

"This book can be recommended as a standard work for all chemists working in the pharmaceutical field, and for everyone else with an interest in the subject." Angew. Chem., Int. Ed. 2004, 43, 544.