3-Methylcholanthrene treatment of C57BL/6N mice induces significant amounts of cytochromes P(1)-450, whereas P(1)-450 levels in 3-methylcholanthrene-treated DBA/2N mice are no different from those in control C57BL/6N or DBA/2N mice. Comparison of 3-methylcholanthrene-treated C57BL/6N and DBA/2N mice -thus provides a convenient means of determining the role of P(1)-450 metabolism in two strains of mice following identical drug treatment regimens. 3-Methylcholanthrene-induced P(1)-450 is shown to be more effective than other forms of P-450 in detoxifying theophylline and zoxazolamine and in enhancing the toxicity of acetaminophen. Cimetidine in vivo blocks these metabolic pathways, resulting in increased toxicity of theophylline and zoxazolamine and protection against acetaminophen toxicity. These data illustrate the double-edged sword nature of P(1)-450 metabolism and the possibility of a paradoxical effect of cimetidine during drug-drug interactions in vivo. Cimetidine is shown to inhibit in vivo and in vitro the metabolism by both 3-methylcholanthrene-induced P(1)-450 and control forms of P-450; these data suggest that cimetidine may be acting at the level of P-450 reduction by NADPH-P-450 oxidoreductase. This same mechanism of action has been previously suggested for ellipticine.

This content is only available via PDF.
Copyright / Drug Dosage / Disclaimer
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.
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 government 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.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.