Introduction to Drug Metabolism

Abstract

This title is available in both hardbound and paperback editions. The paperback edition is sold subject to the condition that it shall not, by way of trade or otherwise, be lent, resold, hired out, or otherwise circulated without the publisher's prior consent in any form of binding or cover other than that in which it is published and without a similar condition including this condition being imposed on the subsequent purchaser.All rights reserved. No part of this book may be reprinted, or reproduced or utilized in any form or by an electronic, mechanical or other means, now PrefaceAlthough the scientific literature on drug metabolism is extensive, it suffers from the disadvantage that the material is diffuse and consists largely of specialist monographs dealing with particular aspects of the subject. In addition, although there are a few excellent texts on drug metabolism in print, these tend to be earlier publications and hence do not take into account the many recent advances in this area. Our motivations for writing this book therefore arose from the clear need for a recent and cohesive introductory text on this subject, specifically designed to cater for the needs of undergraduate and postgraduate students. Much of the subject matter in this text is derived from various courses on drug metabolism given at the University of Surrey and the University of Glasgow to basic science students in pharmacology, biochemistry, nutrition and nursing studies, to pre-clinical medical students and to undergraduate and post-graduate students in toxicology. Therefore, it is our intention that this text will serve as a primer in drug metabolism to a variety of students in the life sciences taking courses in this subject.The term 'drug metabolism' in its broadest sense may be considered as the absorption, distribution, biotransformation and excretion of drugs. To cover all these facets of drug metabolism in a single text is a voluminous task and therefore we have focused primarily on the biotransformation aspects of the subject. Having said this, the text is not solely a list of drug metabolism pathways, but rather it uses biotransformation reactions to rationalize many ix some of their published material. Finally, we express our thanks to the staff of Chapman and Hall for their excellent co-operation and for giving us the opportunity to bring this project to fruition.

Tissue distribution in mice and metabolism in murine and human liver of apigenin and tricin, flavones with putative cancer chemopreventive properties

“…Tissues and plasma were kept at -80°C until analysis, for not longer than 4 weeks, conditions under which we had established that flavones in plasma are completely stable. tissues were isolated, and cytosolic and microsomal protein was quantified, in the usual way [6].…”

Role of the aromatic hydrocarbon receptor in the suppression of cytochrome P-450 2C11 by polycyclic aromatic hydrocarbons

“…If phase I metabolites are sufficiently polar, they may be readily excreted. However, many phase I productç are not eliminated rapidly and undergo a subsequent phase II reaction in which a substrate such as glucuronic acid, sulfate, acetate, glutathione or an amino acid combines with the newly established functional group to from a highly polar conjugate which is readily eliminated (Gibson and Skett, 1994;Katzung, 1995;Ortiz de Montellano, 1995). The majority of phase I reactions are carried out by the cytochrome P450 superfamily of enzymes.…”

Preparation of human drug metabolites using fungal peroxygenases

“…They are frequently used as substrates and authentic standards in studies of drug bioavailability, pharmacodynamics and pharmacokinetics [1][2][3]. In vivo, the C-H bonds of pharmaceuticals are predominantly oxygenated by liver cytochrome P450-monooxygenases (P450s) to yield more polar HDMs that are excreted directly or as conjugates [4]. This directed incorporation of an oxygen atom into a complex organic structure is one of the most challenging reactions in synthetic organic chemistry [5] and thus low yields and the need for laborious removal of byproducts have prevented the cost-effective preparation of HDMs by purely chemical methods [6].…”