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      Effect of Single Oral Dose of Aspirin on Human Platelet Functions and Plasma Plasminogen Activator Inhibitor-1

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          Abstract

          Previous reports documented the inhibitory efficacy of different doses of aspirin on arachidonic acid (AA)-induced platelet aggregation, however, the sensitivity of platelets toward other agonists as well as the effects of aspirin on platelet and plasma plasminogen activator inhibitor-1 (PAI-1) release and levels were not investigated. Hence, the present study was undertaken to investigate the effect and duration of action of a single oral dose (650 mg) of aspirin on human platelet functions (n = 34, normal healthy male and female volunteers) including aggregation, fibrinogen binding and PAI-1 release, and on the plasma level of PAI-1. Aspirin demonstrated a rapid onset of action (at 2 h after ingestion) in specifically inhibiting ex vivo AA-mediated functions including (a) fibrinogen binding to gel-purified platelets, (b) platelet aggregation, and (c) platelet PAI-1 release. A peak reduction of plasma PAI-1 level at 2 h was demonstrated as well. The effect of aspirin on the ex vivo AA-mediated effects (a-c) was shown to last for up to 4 days. However, aspirin treatment resulted in a rebound effect in platelet function (a-c) to other platelet agonists such as adenosine diphosphate or the combination of agonists including adenosine diphosphate, epinephrine, and AA. In conclusion, a single oral dose of aspirin has long-lasting effects on AA-induced platelet activation and reduces plasma levels of PAI-1 as well. The rebound effect of platelets in response to other agonists suggests the potential usefulness of a combination therapy of aspirin with other antiplatelet drugs, as well as the potential advantages for other platelet inhibitors such as GpIIb/IIIa receptor antagonists.

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          Author and article information

          Journal
          CRD
          Cardiology
          10.1159/issn.0008-6312
          Cardiology
          S. Karger AG
          0008-6312
          1421-9751
          1993
          1993
          18 November 2008
          : 83
          : 5-6
          : 367-373
          Affiliations
          DuPont Merck Pharmaceutical Company, Cardiovascular Diseases Division, Exp. Station, Wilmington, Del., USA
          Article
          175993 Cardiology 1993;83:367–373
          10.1159/000175993
          8111770
          © 1993 S. Karger AG, Basel

          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.

          Page count
          Pages: 7
          Categories
          Clinical Pharmacology

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