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      Avoiding Acyclovir Neurotoxicity in Patients with Chronic Renal Failure Undergoing Haemodialysis

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          Abstract

          Acute neurotoxicity following the administration of the recommended oral dose of acyclovir (800 mg twice daily) to dialysis-dependent patients is increasingly recognised. This suggests that the recommended dose is too high. Little is known of the pharmacokinetics of oral acyclovir in dialysis patients. We studied 7 patients with oliguric end stage renal failure receiving haemodialysis. Following haemodialysis, each patient received a single 800-mg tablet of acyclovir. Plasma acyclovir levels were monitored over the next 48 h as well as before and after the next routine dialysis. Peak plasma levels were achieved at 3 h (12.54 ± 1.76 μ M, range 8.5-17.5 μM) with the half-life calculated to be 20.2 + 4.6 h. Mean plasma levels of 6.29 ± 0.94 μ M were within the quoted range to inhibit herpes zoster virus (4-8 μ M) at 18 h. Haemodialysis (4-5 h) eliminated 51 ± 11.5% of the acyclovir which remained at 48 h. Computer modelling of various dose modifications suggests that a loading dose of 400 mg and a maintenance dose of 200 mg twice daily is sufficient to maintain a mean plasma acyclovir level of 6.4 ± 0.8 μ M. A further loading dose (400 mg) after dialysis would raise the residual acyclovir concentration by 6.1 ± 1.0 μ M. Such a dose modification should prevent neurotoxicity, whilst the rapid elimination of acyclovir by a single haemodialysis treatment provides both a diagnostic and therapeutic tool when toxicity is suspected.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1995
          1995
          17 December 2008
          : 69
          : 4
          : 428-432
          Affiliations
          aDepartment of Nephrology, Royal London Hospital, London, and bCentre of Pharmacy Practice, School of Pharmacy, University of London, UK
          Article
          188514 Nephron 1995;69:428–432
          10.1159/000188514
          7777108
          © 1995 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: 5
          Categories
          Original Paper

          Cardiovascular Medicine, Nephrology

          Acyclovir, Neurotoxicity, Haemodialysis

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