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      Pharmacokinetics and Retinal Toxicity of Intravitreal Liposome-Encapsulated 5-Fluorouridine

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          Abstract

          Background: Fluoropyrimidines may be effective in preventing proliferative vitreoretinopathy after repair of complicated retinal detachments. Liposome encapsulation of these antiproliferative drugs may extend the intravitreal half-life and increase their efficacy. Methods: The current study evaluated the pharma-cokinetic behavior of intravitreally injected 5-fluorouridine (5-FUR), free and encapsulated in liposomes, either conventionally or coated with collagen into 25 New Zealand rabbits. Additionally, we investigated the retinal toxicity of intravitreal injections of 100, 250 and 500 µg as well as 1 mg 5-FUR as free drug or encapsulated in liposomes in the rabbit eye. Results: The half-life of free 5-FUR after liposome injection into the vitreous cavity was 18.17+2.43 h, considerably longer than the half-life of free 5-FUR (0.82 h). Electrophysiologic tests did not show any changes in latency and a-wave amplitude and minimal changes in the b-wave amplitude. Histopathologic studies revealed integrity of the inner limiting membrane, and mild vacuolization in the outer retina. Conclusion: Encapsulation of 5-FUR within liposomes markedly increases its intravitreal half-life. Our study suggests that liposome-encapsulated 5-FUR is not toxic to the retina even at doses of 1 mg.

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          Author and article information

          Journal
          OPH
          Ophthalmologica
          10.1159/issn.0030-3755
          Ophthalmologica
          S. Karger AG
          0030-3755
          1423-0267
          1997
          1997
          01 April 2010
          : 211
          : 6
          : 344-350
          Affiliations
          aHospital Universitario Valle Hebron, Universidad Autónoma de Barcelona, bUniversidad Central de Barcelona, cConsejo Superior Investigaciones Científicas, Barcelona, y dUnidad de Biología Celular, Universidad Central de Barcelona, España
          Article
          310826 Ophthalmologica 1997;211:344–350
          10.1159/000310826
          9380351
          © 1997 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
          Original Paper

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