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      Kinetics of Aluminoxamine and Feroxamine Chelates in Dialysis Patients

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          Abstract

          To achieve a rational basis for the use of deferoxamine (DFO) in aluminum (AL) – and iron (Fe) – overloaded uremic patients, important insights may be provided by the recently available micromethods to determine DFO and its metallochelates aluminoxamine (AlA) and feroxamine (FeA). With this procedure, AlA and FeA plasma kinetics were evaluated in a pilot study in 10 uremic patients during a whole week after a single DFO infusion performed during the first hour of the first standard bicarbonate hemodialysis (HD) of the week. Patients were divided into normal (n = 6) and high (n = 4) ferritin groups (1 and 2 respectively). Baseline Al concentrations were > 2 < 6 in group 1 and < 1.5 μmol/l in group 2. DFO was given at doses of 40, 20 and 10 mg/kg. AlA and FeA showed substantially different kinetics. AlA kinetics were similar in group 1 and 2: they reached their peak at the beginning of the 2nd HD, decreased during the 2nd and 3rd HD, and with the highest DFO dose still increased between the 2nd and 3rd HD. At similar pre-DFO Al values ( > 2 < 3.3 μmol/l), increased DFO doses produced increased AlA concentrations ranging from 95 to 40% of total plasma Al for all the week. At higher pre-DFO Al values ( > 3.5 < 6 μmol/l), even a DFO dose as low as 10 mg/kg was sufficient to form consistent AlA amounts (from 80 to 15% of total Al). Also FeA kinetics were similar in group 1 and 2, but in this case, the peak was reached during the first HD, with an ensuing progressive decrease during all the interdialysis periods and HD times. FeA dropped in both groups from about 90-85% to 20-10% of plasma Fe at the beginning of the 2nd HD. A substantial increase in total plasma Fe differentiated group 2 from group 1. Mild differences only were observed with different DFO doses in group 2. Discrepancies between AlA and FeA on one hand, and plasma Al and Fe increase on the other, clearly showed that both circulating Al and Fe contributed to form metallochelates. The implications for clinical practice are that DFO once a week provides substantial Al mobilization and removal and sparse Fe loss in normal iron statues patients, while moderate repeated DFO doses permit Fe removal in iron-overloaded patients.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1992
          1992
          11 December 2008
          : 60
          : 4
          : 411-417
          Affiliations
          aDepartment of Nephrology, University of Torino, S. Giovanni-Molinette Hospital, Torino; Services of Nephrology, Hospital of bChietiand cAsti; dPMP Chemistry Section, Venezia, Italy
          Article
          186800 Nephron 1992;60:411–417
          10.1159/000186800
          1584315
          © 1992 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

          Cardiovascular Medicine, Nephrology

          Deferoxamine, Metallochelates, Aluminoxamine, Feroxamine

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