The Textbook Of Pharmaceutical Medicine Fourth Edition

The Textbook of Pharmaceutical Medicine, Fourth Edition John P. Griffin John O' Grady, editors BMJ Books The Textbook of Pharmaceutical Medicine Fourth edition Edited by John P Griffin BSc, PhD, MBBS, FRCP, FRCPath, FFPM Chairman, John Griffin Associates Ltd. Director, Pharmadiligence Ltd. Visiting Professor, University of Surrey Postgraduate Medical School Former Director, Association of the British Pharmaceutical Industry, London Formerly Professional Head of the Medicines Division, DHSS, London and John O’Grady MD, FRCP, FFPM, FBIRA, MRCPath Medical Director for Europe, Daiichi Pharmaceutical Co. Ltd., London Visiting Professor of Clinical Pharmacology, University of London  BMJ Books 2002 BMJ Books is an imprint of the BMJ Publishing Group All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording and/or otherwise, without the prior written permission of the publishers. First published by BMJ Books in 2002 BMA House, Tavistock Square, London WC1H 9JR All previous three editions were published by The Queen’s University of Belfast First edition published in 1993 Second edition published in 1994 Third edition published in 1998 www.bmjbooks.com British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 0 7279 1523 1 Typeset by SIVA Math Setters, Chennai, India Printed and bound by MPG Books, Bodmin, Cornwall Contents Contributors Preface v viii Acknowledgements ix The editors x Part I: 1 Research and development 1 Discovery of new medicines Anand S Dutta 3 2 Pharmaceutical development Gavin Halbert 96 3 Toxicity testing David J Tweats, M David C Scales 128 4 Exploratory development John Posner 170 5 Clinical pharmacokinetics Paul Rolan 214 6 Clinical trials and good clinical practice Nigel Baber, John Sweatman 247 7 Medical statistics Kenneth D MacRae 358 8 Development of medicines: full development Alan G Davies, Peter D Stonier 395 Part II: 9 10 Medical department issues 421 The medical department Darrall L Higson 423 Medical marketing John H Young 436 iii CONTENTS 11 Information and promotion D Michael Humphreys 456 12 The supply of unlicensed medicines for particular patient use John O’Grady, Amanda Wearing 491 13 Legal and ethical issues relating to medicinal products Christine H Bendall, Christopher JS Hodges 503 14 The safety of medicines A Peter Fletcher, Susan Shaw 532 Part III: 15 16 17 18 19 Regulatory aspects The development of the control of human medicines in Europe from classical times to the year 2000 John P Griffin, Rashmi R Shah Technical requirements for registration of pharmaceuticals for human use: the ICH process and the common technical document Patrick F D’Arcy, Dean WG Harron The regulation of drug products by the United States Food and