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Vol. 28, No. 5, 1984
Issue release date: 1984
Section title: Original Paper
Pharmacology 1984;28:296–300
(DOI:10.1159/000137977)

Effect of Biological Time on the Determination of the LD50 of 5-Fluorouracil in Mice

Burns E.R. · Beland S.S.
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock, Ark., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 7/13/1983
Accepted: 8/23/1983
Published online: 6/4/2008
Issue release date: 1984

Number of Print Pages: 5
Number of Figures: 0
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: http://www.karger.com/PHA

Abstract

The LD50 was determined for 5-fiuorouracil (FU) in mice at 11.00 and 23.00 h during one 24-hour period. These times were chosen because in mice kept on a light-dark cycle, with lights on from 06.00 to 18.00 h, the natural circadian rhythm in DNA synthetic activity in many different normal organs attains peak levels around 24.00 h (mid-dark) and through levels around 12.00 h (mid-light). The LD50 of FU, in milligrams per kilogram body weight, was much higher (450–500 mg/kg) at 11.00 than at 23.00 h (250–300 mg/kg). Since the biology of the living animal oscillates significantly on a daily or circadian basis, it is understandable that the degree of susceptibility or resistance to drugs should also fluctuate over the circadian period. Determination of the LD50 of a drug at that point in time when the animal is naturally resistant to that drug will result is a false appraisal of the toxic effects to the drug. To assess correctly the risk a drug poses, it should be tested at its time of maximal susceptibility in the living animal.

© 1984 S. Karger AG, Basel


  

Author Contacts

E.R. Burns, Department of Anatomy, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (USA)

  

Article Information

Received: July 13, 1983
Accepted: August 23, 1983
Published online: June 04, 2008
Number of Print Pages : 5

  

Publication Details

Pharmacology (International Journal of Experimental and Clinical Pharmacology)

Vol. 28, No. 5, Year 1984 (Cover Date: 1984)

Journal Editor: Donnerer J. (Graz), Billingsley M.L. (Hershey, Pa.), Maeyama K. (Matsuyama)
ISSN: 0031–7012 (Print), eISSN: 1423–0313 (Online)

For additional information: http://www.karger.com/PHA


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 7/13/1983
Accepted: 8/23/1983
Published online: 6/4/2008
Issue release date: 1984

Number of Print Pages: 5
Number of Figures: 0
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: http://www.karger.com/PHA


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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