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      Pharmacokinetics and Metabolism of Tiapamil


      S. Karger AG

      Pharmacokinetics, Metabolism, Verapamil, Tiapamil

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          The main pathways of biotransformation of tiapamil and basic pharmacokinetic information on the drug are presented and compared with those of verapamil. Both compounds are metabolized by similar pathways consisting mainly of N- and O-dealkylation. In man, the two main metabolites of tiapamil in blood and urine are the N-desmethyl derivative and the other secondary amine which has lost the dimethoxyphenethyl-moiety. Both metabolites have low pharmacological activity and do not contribute significantly to the effect of the parent drug. Analysis of single intravenous doses of 10 and 50 mg revealed that tiapamil has pharmacokinetic parameters very similar to those of verapamil, the total plasma clearances for both compounds being about 800 ml/min. Due to its somewhat smaller volume of distribution (twice body weight), tiapamil has a slightly shorter half-life of elimination from plasma [t½β] – 2.5 h – than does verapamil (4 h). On oral dosing, however, both drugs have substantially reduced bioavailability of about 20%, this being due to extensive first-pass metabolism rather than to incomplete absorption. Tiapamil plasma levels following intravenous infusion or multiple oral dosing may be predicted from basic pharmacokinetic parameters with reasonable accuracy. Neither tiapamil nor its metabolites tend to accumulate on repeated oral dosing of 200 mg tiapamil t.i.d. Though both tiapamil and verapamil are metabolized extensively, and only a small proportion of the dose is excreted unchanged, large differences exist with respect to the route of excretion. While the metabolites of verapamil are excreted largely (70% of the dose) in the urine after both intravenous and oral dosing, the metabolites of tiapamil are excreted largely in the faeces: 66% after intravenous administration and 90% after oral dosing.The following concept is proposed: Following oral administration, both drugs are rapidly and completely absorbed. They are subject to extensive first-pass metabolism involving gut and liver. While the metabolites of verapamil enter the systemic circulation and are excreted mainly by the kidneys, the metabolites of tiapamil are directly secreted into the bile and excreted in the faeces, thus bypassing the systemic circulation. This may have clinical consequences with respect to tolerance and safety of the drug.

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          Author and article information

          S. Karger AG
          07 November 2008
          : 69
          : Suppl 1
          : 68-78
          Biological Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd., Basel, Switzerland
          173539 Cardiology 1982;69:68–78
          © 1982 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: 11
          Preclinical Data


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