CHEMOTHERAPY Volume 4 Pharmacology of Antibiotics CHEMOTHERAPY Volume 1 Clinical Aspects of Infections Prophylaxis; life-threatening infections; infection in leukaemia; surgical infection; anaerobic infection; respiratory and urinary tract infections; amikacin. Volume 2 Laboratory Aspects of Infections Sensitivity testing; assay methods; animal models of infection; sisomycin; tobramycin_ Volume 3 Special Problems in Chemotherapy Tuberculosis; genital tract infections; antibiotic resistance and mode of action; topical chemotherapy and antisepsis_ Volume 4 Pharmacology of Antibiotics Tissue concentrations; pharmacokinetics; untoward effects of antibiotics. Volume 5 Penicillins and Cephalosporins Penicillins and cephalosporins; betalactamases; new agents. Volume 6 Parasites, Fungi, and Viruses Parasitic infections; fungal infections; chemotherapy of viruses; co-trimoxazole. Volume 7 Cancer Chemotherapy I Symposia - new drugs and approaches; cell and pharmacokinetics; potentiators of radiotherapy; in vitro screening systems; immunological aspects. Volume 8 Cancer Chemotherapy II Free papers - new drugs and approaches; cell and pharmacokinetics; mechanisms of action; new analogues; cancer chemotherapy of specific organs. CHEMOTHERAPY VoluIlle 4 Pharmacology of Antibiotics Edited by 1. D Williams The London Hospital Medical CoUege London, U. K. and A.M. Geddes East Birmingham Hospital Birmingham, u.K. Plenum Press· New York and London Library of Congress Cataloging in Publication Data International Congress of Chemotherapy, 9th, London, 1975. Pharmacology of antibiotics. (Chemotherapy;v.4) 1. Antibiotics - Congresses. 2. Antibiotics - Side effects - Congresses. I. Williams, John David, M.D. II. Geddes, Alexander McIntosh. III. Title. IV. Series. RM260.2.C45 vol. 4 [RM265.2] 615'.585 [615'.329] 76-1946 Proceedings of the Ninth International Congress of Chemotherapy held in London, July, 1975 will be published in eight volumes, of which this is volume four. ISBN 978-1-4684-3125-4 ISBN 978-1-4684-3123-0 (eBook) DOl 10.1007/978-1-4684-3123-0 ©1976 Plenum Press, New York Softcover reprint of the hardcover I st edition 1976 A Division of Plenum Publishing Corporation 227 West 17th Street, New York, N.Y. 10011 United Kingdom edition published by Plenum Press, London A Division of Plenum Publishing Company, Ltd. Davis House (4th Floor), 8 Scrubs Lane, Harlesden, London, MWI0 6SE, England All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher CHEMOTHERAPY Proceedings of the 9th International Congress of Chemotherapy held in London, July, 1975 Editorial Committee K. Hellmann, Chairman (Anticancer) Imperial Cancer Research Fund, London. A. M. Geddes (Antimiaobial) J. D. Williams (Antimiaobial) East Birmingham Hospital The London Hospital Medical CoUege. Congress Organising Committee W. Brumfitt I. Phillips H.P. Lambert K. Hellmann M.R.W. Brown P. Turner K.D. Bagshawe D.G.James A.M. Geddes H. Smith C. Stuart-Harris D.Armitage EJ. Stokes R.G.Jacomb D.Crowther F. Wrigley D.T.D. Hughes D.8. Reeves J.D. Williams T.Connors R.E.O. Williams International Society of Chemotherapy Executive -to July 1975 P.Malek H.P. Kuemmerle H. Ericsson C. Grassi Z.Modr G.M. Savage G.H. Werner K.H. Spitzy H. Umezawa P. Rentchnick Preface The International Society of Chemotherapy meets every two years to review progress in chemotherapy of infections and of malignant disease. Each meeting gets larger to encompass the extension of chemotherapy into new areas. In some instances, expansion has been rapid, for example in cephalosporins, pen icillins and combination chemotherapy of cancer - in others slow, as in the field of parasitology. New problems of resistance and untoward effects arise; reduction of host toxicity without loss of antitumour activity by new substances occupies wide attention. The improved results with cancer chemotherapy, es pecially in leukaemias, are leading to a greater prevalence of severe infection in patients so treated, pharmacokinetics of drugs in normal and diseased subjects is receiving increasing attention along with related problems of bioavailability and interactions between drugs. Meanwhile the attack on some of the major bacterial infections, such as gonorrhoea and tubercu losis, which were among the first infections to feel the impact of chemotherapy, still continue to be major world problems and are now under attack with new agents and new methods. From this wide field and the 1,000 papers read at the Congress we have produced Proceedings which reflect the variety and vigour of research in this important field of medicine. It was not possible to include all of the papers presented at the Congress but we have attempted to include most aspects of cur rent progress in chemotherapy. We thank the authors of these communications for their cooperation in enabling the Proceedings to be available at the earliest possible date. The method of preparation does not allow for uniformity of typefaces and presentation of the mate rial and we hope that the blemishes of language and typographical errors do not detract from the understanding of the reader and the importance of the Proc~edings. K. HELLMANN, Imperial Cancer Research Fund A. M. GEDDES, East Birmingham Hospital J. D. WILLIAMS, The London Hospital Medical College vii Contents Tissue Binding of Antibiotics • • • • • • • • • • • • • • •• 1 C. M. Kunin The In Vivo Significance of Antibiotics in the Tissues 7 H. Mattie Antibiotic Concentrations in Human Interstitial Fluid • • •• 13 J. S. Tan Antibiotic Activities Inside Leucocytes • • • • 17 J. A. Raeburn, E. Watson, E. J. Hanson, and T. Johnston Antibiotic Concentrations in Sinus Secretions • . • • • • •• 25 A.-S. Malmborg Antibiotics in Respiration Secretions in the Experimental Animal • • • • • • • • • 35 J. E. Pennington Antibiotic Concentrations in the Human Bone Marrow and Bone Marrow Hematoma • • • • • • • • • 43 S. Kondo Passage of Doxycycline into the Thoracic Duct urmPh after Oral and Intravenous Administration in Man 47 P.-A. ~dh, K.-E. Andersson, H. Dencker, and M. herlund Concentration of Antibacterials in Human Seminal Plasma 53 A.-S. Malmborg, K. Dornbusch, R. Eliasson, and C. Lindholmer Antibiotic Concentrations in Intracranial Pus: A Study from a Collaborative Project • • • • 61 J. de Louvois and R. Hurley ix x CONTENTS Concentrations o~ Antibiotics in Bronchiolar Secretions o~ the Patients with Chronic Respiratory In~ections • • • • • • • • 73 K. Matsumoto and Y. Uzuka Further Studies on the Protein Binding Inhibitor o~ Antimicrobials in Uremic Sera • • • • • • • 79 W. A. Craig Antimicrobial Therapy in Patients on Haemodialysis 85 J. Verhoe~ and P. L. Oe Ageing and Antimicrobial Therapy 93 P. L. Oe and J. Verhoe~ Pharmacokinetics o~ Carbenicillin Through Di~~erent Dialysis Membranes • • • • • 101 G. Naumann, M. Holtz, W. MUntner, W. Nimmrich, E. Budde, and H. Klinkmann The E~~ect o~ pH on the Transport o~ Oligosaccharidic Antibiotics Across a Membrane Model System 107 L. Favalli, M. C. Chiari, A. Rozza, and F. Piccinini Prolonged Excretion o~ Gentamicin in Patients with Normal Renal Function • • • • • • 115 G. Kahlmeter, T. Hallberg, S. Jonsson, C. Kamme, and B. Ursing The Use o~ Gentamicin in Patients with Impaired Renal Function • • • • • • • • • • • • • 121 J. L. Anderton, E. Hanson, and J. A. Raeburn Comparative Biliary Excretion o~ Ampicillin, Metampicillin, and Carbenicillin 127 M. Pinget, J. M. Brogard, and J. Lavillaureix Sisamicin: Serum Hal~-Li~e and Distribution Space in Patients with Normal and Impaired Renal Function 141 S. Roth, K. G. Naber, M. Scheer, and H. Lange Serum Levels o~ Nalidixic Acid in Patients with Impaired Renal Function • • • • • • • • • • • • • • • 151 G. Gundlach, G. Linzenmeier, and P. Bruehl Biotrans~ormation o~ the Antibiotics in the Patients and Animals with Liver Impairment ••••• 159 O. Kunii, K. Fukaya, and K. Mashimo CONTENTS xi Comparative Pharmacokinetics of Cephalosporins 165 V. P. Jakovlev, V. S. Klimova, and E. A. Rudzit Ten Years' Experience with the Blood Level Duration Test 171 J. Bang Statistical Aspects of the Blood-Level Duration Test 177 M. W. Bentzon Effect of Recumbency on Erythromycin Absorption • • • • • • • 183 R. L. Parsons and G. M. Paddock Cholestyramine Induced Antibiotic Malabsorption 191 R. L. Parsons, G. M. Paddock, and G. M. Hossack Investigation of the Gastrointestinal Absorption of Ampicillin, Cephalexin, and Pivampicillin • 199 H. Lode Comparative Bioavailability of Oral Ampicillin Suspension, Pivampicillin Hydrochloride Salt (Capsule), Pivampicillin Pamoate Salt (Suspension) and Pivampicillin Probenecid Salt (Tablet) in Man • • • • • • • • • • • • • • •• 205 G. Hitzenberger, P. E. Wittreich, I. Jaschek, A. Korn, J. Bonelli, and D. Magometschnigg Biotransformation of Ampicillin, Amoxicillin and Oxacillin in Healthy Subjects and in Patients with Bacteriuria • • • • • • • • • • 213 H. Graberm, T. Perenyi, M. Arr, and E. Ludwig Antibiotic Absorption in Crohn's Disease 219 R. L. Parsons, G. M. Paddock, G. M. Hossack, and D. M. Hailey A Pharmacokinetic Study of the Combination Rifampicin Plus Trimethoprim in Man • • • • • 231 W. Brumfitt, V. M. Moss, E. Brooker, and J. M. T. Hamilton-Miller The Excretion and Metabolism of Talampicillin in Rat, Dog, and Man ••••••••••••• 237 D. J. Jeffery, K. H. Jones, and P. F. Langley The Excretion of Hetacillin Methoxymethyl Ester (BL-P176l) into the Prostatic Fluid of the Dog 243 T. B. Kjaer and P. O. Madsen xii CONTENTS Kidney Distribution of Carbenicillin, Indanyl Carbenicillin, Tobramycin, Fosfomycin, and Cefazolin • • • • • • • • • • • • 249 R. di Carlo, D. Savoia, G. Fontana, and G. Ceccarelli Studies on Tissue Distribution of Antibiotics - An Attempt to Estimate Tissue Levels from Macro-Autoradiograms • • • • • • 255 J. Shimada, Y. Ueda, M. Saigusa, and R. Tsukuda Immune Responsiveness to a-Lactam Antibiotics 261 J. M. Dewdney and B. Weston Rifampicin-Induced Antibodies 273 S. Worlledge Possible Mechanisms in Pathogenesis of NitrofUrantoin-Induced Lung Disease 279 P. Cole Assessing Untoward Effects 287 A. Herxheimer Antimicrobial Usage in the U. S. A. 293 W. A. Craig and K. P. Sarver Prospects for Control of Antibiotic Usage • • • • • . • • • • 299 C. M. Kunin Antibiotic Induced Diarrhoea and Colitis in Orthopaedic In-Patients • • • • • • • • • • • • • • • • • • 307 R. L. Parsons, J. Salfield, and J. P. Beavis Abnormalities in the Fecal Flora of Subacute Myelo-Optic Neuropathy (SMON) Patients and Effects of Clioquinols on Human Intestinal Flora • • • • • • • • • • • 315 R. Nakaya, H. Inugami, T. Mitsuoka, andA. Igata Effect of Chloramphenicol on Phagocytic Activity in Human Polymorphonuclear Cells • • • • • • • 321 N. Ki tani and Y. Kokubun The Effect of Rifampicin on Plasma Glutamyl Transpeptidase, Salicylamide Glucuronide Formation and D-Glucaric Acid Excretion • 327 K. Malaka-Zafiriu, G. Katzos, J. Sotiriu, B. Danielides, and Chr. Cassimos