We studied the anti-inflammatory activity of meloxicam on rat carrageenin-induced pleurisy and its toxicity for rat gastric mucosa, relative to its in vitro inhibitory potency against partially purified cyclooxygenase (COX)-1 and COX-2 preparations in order to clarify the pharmacological profile of the compound as an anti-inflammatory agent. In rat carrageenin-induced pleurisy, the plasma exudation rate peaked at 5 h, at which time COX-2 was detectable in cells from the pleural exudate. Meloxicam and piroxicam (1 and 3 mg/kg) and NS-398 (3 mg/kg) showed almost equal anti-inflammatory potency against 5-hour pleurisy. A single oral administration of the compounds caused a dose-dependent increase in the number of rats with gastric mucosal erosion. The ED50 value for meloxicam (5.92 mg/kg) was significantly higher than that for piroxicam (1.76 mg/kg), indicating that meloxicam is safer. Indometacin showed intermediate safety (2.59 mg/kg). In in vitro experiments, indometacin inhibited COX-1 about 1.7 times more potently than COX-2. NS-398 inhibited COX-2 with an IC50 of 0.32 µM, but never affected COX-1 activity, even at 100 µM. In the same assay system, meloxicam inhibited COX-2 about 12 times more selectively than COX-1. Piroxicam, however, inhibited both isoforms almost equally. These results indicate that meloxicam is a potent anti-inflammatory agent with low gastric toxicity. One reason for its in vivo pharmacological profile may be related to its relative selectivity for COX-2 over COX-1. Thus, meloxicam may belong to a group of COX-2 selective anti-inflammatory agents with a better safety profile than conventional COX-1 and COX-2 nonselective anti-inflammatory agents.

Keywords:
Meloxicam, Carrageenin-induced pleurisy, Cyclooxygenase-2 Gastric toxicity of NSAIDs
This content is only available via PDF.
© 1997 S. Karger AG, Basel
1997
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.