Open Access Medical Books

TEXTBOOK : TOPICS ON DRUG METABOLISM

DRUG METABOLISM

Edited by James Paxton .

306 pages .
Open Access .


For most drugs, metabolism plays a central role in defining their concentration time profile in the body and, consequently, the magnitude and duration of their pharmacological response. The duration of action of most drugs is terminated by removal of the drug from the site of action. A few drugs are polar in nature and are readily eliminated in the urine by the kidney. However, most drugs are relatively lipid soluble and would remain in the body for months, if not years, if they were not metabolized. Most drugs undergo one or more metabolic reactions. They are most often converted to more polar derivatives, favoring excretion in the urine or bile. Thus, drug metabolism is an important determinant of the duration and extent of the pharmacological response, and is arguably the main factor in determining the extensive inter-individual variability observed in the response to drugs in a patient population.
In the development of any new drug, it is highly likely that drug metabolism will play a crucial part. Although new therapeutic entities are designed and initially selected for their pharmacodynamic properties, inappropriate metabolism may often lead to their demise, either during their clinical trials, or even after their introduction to the marketplace. It is essential that investigations of the possible metabolic fate of a new drug candidate are undertaken early in its preclinical development to avoid such failures. Over the last twenty years, 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. These efforts are made in order to avoid latestage drug failure due to such factors as undesirable metabolic instability, toxic metabolites, drug-drug interactions, or polymorphic and saturation metabolism. As a result, it is becoming apparent that a diminishing number of drugs are now being withdrawn during clinical studies and from the marketplace on account of inappropriate metabolism and pharmacokinetics.
The objective of this book is to present some in-depth reviews of selected topics in Drug Metabolism. These reviews range from the enzymes involved and their regulation, to leading-edge in vitro and in vivo techniques being used and developed for the prediction of the metabolic parameters and profiles of potential new drug candidates. Topics covered include: 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.

Dr. James Paxton
University of Auckland,
New Zealand




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CONTENTS of the textbook :




 1 Oral Absorption, Intestinal Metabolism and Human Oral Bioavailability 1 Ayman El-Kattan and Manthena Varma

 2 Phase II Drug Metabolism 35 Petra Jančová and Michal Šiller

 3 Pharmacogenetics and Metabolism: Past, Present and Future 61 Fabricio Rios-Santos and Luiz Alexandre V. Magno

 4 Genetic and Epigenetic Factors Affecting Cytochrome P450 Phenotype and Their Clinical Relevance 87 Viola Tamási and András Falus

5 Altered Drug Metabolism and Transport in Pathophysiological Conditions 111 Adarsh Gandhi and Romi Ghose

 6 Anticancer Drug Metabolism: Chemotherapy Resistance and New Therapeutic Approaches 137
Hanane Akhdar, Claire Legendre, Caroline Aninat and Fabrice Morel

 7 Transcription Factors Potentially Involved in Regulation of Cytochrome P450 Gene Expression 171 Piotr Czekaj and Rafał Skowronek

8 Determination of Cytochrome P450 Metabolic Activity Using Selective Markers 191 Jan Jurica and Alexandra Sulcova

 9 Electrochemical Methods for the In Vitro Assessment of Drug Metabolism 221 Alejandro Álvarez-Lueje, Magdalena Pérez and Claudio Zapata

10 Microdosing Assessment to Evaluate Pharmacokinetics and Drug Metabolism Using Liquid Chromatography-Tandem Mass Spectrometry Technology 247 Jinsong Ni and Josh Rowe

 11 Label-Free Quantitative Analysis Using LC/MS 265 Atsumu Hirabayashi

 12 Recent Advances in Pharmacogenomic Technology for Personalized Medicine 281 Toshihisa Ishikawa and Yoshihide Hayashizaki .






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Published by: younes younes - Monday, March 25, 2013

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