Pharmacology

Original Paper

Dose-Dependent Pharmacokinetics of a Xanthine-Related Nootropic Drug, Ethimizol, in Rats

Trnovec T.a · Ďurišová M.a · Burdátš P.a · Šoltés L.a · Kállay Z.a · Bezek Š.a · Piotrovskii L.B.b

Author affiliations

aInstitute of Experimental Pharmacology, Centre of Physiological Sciences, Slovak Academy of Sciences, Bratislava, Czechoslovakia; bInstitute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad, USSR

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Pharmacology 1987;34:149–156

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 15, 1986
Accepted: September 13, 1986
Published online: June 05, 2008
Issue release date: 1987

Number of Print Pages: 8
Number of Figures: 0
Number of Tables: 0

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

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

Abstract

Pharmacokinetics of the respiratory analeptic ethimizol, 4,5-bis(methylcarba-moyl)-1-ethylimidazole, with recently recognized nootropic properties, its metabolite 4-carbamoyl-5-methylcarbamoyl-1-ethylimidazole and of two metabolites of unknown structure was studied in plasma of rats after intravenous administration of the [2-14C]-labelled compound in 5 doses: 1.1, 3.3, 10, 20, and 30 mg/kg. The apparently monoexponential time course of dose normalized ethimizol plasma concentrations were not superimposable and the derived pharmacokinetic parameters were dose-dependent. The elimination rate constant and the initial volume of distribution decreased with increasing dose. The AUC versus dose relationship displayed disproportionate increases with increasing dose. Plasma ethimizol failed to obey the Michaelis-Menten kinetics and in an attempt to rationalize the observed nonlinearity a complete competitive product inhibition was suggested. Similar to the parent drug, the three metabolites exhibited a dinstinctly dose-dependent behavior as could be deduced from their dose-normalized concentration-time curves.

© 1987 S. Karger AG, Basel




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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 15, 1986
Accepted: September 13, 1986
Published online: June 05, 2008
Issue release date: 1987

Number of Print Pages: 8
Number of Figures: 0
Number of Tables: 0

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

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


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.
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