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      F HD: An Index to Evaluate Drug Elimination by Hemodialysis

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          Abstract

          Background: In hemodialyzed patients, physicians have to (1) adjust drug dosage for a creatinine clearance lower than 10–15 ml/min and (2) know whether or not the drug will be removed by the dialysis session to decide whether it may be administered before or after the session on dialysis days. However, of several indices being used to evaluate drug removal by dialysis none is appropriate and we suggest a novel index named F<sub>HD</sub>, which reflects the role of hemodialysis clearance of a drug in its overall clearance during the session. Methods: Pharmacokinetic simulations were performed to test the influence of dialysis on the pharmacokinetics of some drugs, whether F<sub>HD</sub> was considered or not, to determine when to administer the drug. F<sub>HD</sub> was then calculated for several drugs and its value compared with other indices. Five hemodialysis patients from our department for whom the time of drug administration was determined according to F<sub>HD</sub> were included in a small study and their drugs’ trough concentrations were monitored. Results: F<sub>HD</sub> emphasized that considering hemodialysis clearance alone may lead to false interpretations of the potential dialyzability of some drugs. In our patients, who received their treatment according to the ‘F<sub>HD</sub> rule’, monitoring of trough levels gave satisfactory results. Conclusion: The use of the ‘F<sub>HD</sub> rule’ should be tested on a long-term administration basis to confirm our conclusion. F<sub>HD </sub>could be the index of choice to determine when to administer a drug, before or after the session, in hemodialysis patients.

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          Most cited references 22

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          Dosing guidelines for fluconazole in patients with renal failure.

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            Drug dosage in patients during continuous renal replacement therapy. Pharmacokinetic and therapeutic considerations.

            The advantages of continuous haemofiltration and haemodialysis over intermittent haemodialysis for the treatment of acute renal failure are well recognised. In intensive care patients, 4 different continuous procedures, arteriovenous and venovenous haemofiltration (CAVH and CVVH) or haemodialysis (CAVHD and CVVHD), are employed. These effective detoxification treatments require knowledge of their influence on drug disposition. Data on kinetics of drugs during continuous treatment are scarce and limited almost exclusively to the oldest and least effective procedure (CAVH). Selected dialysis membranes may adsorb drugs, as in the case of aminoglycosides. In addition, elimination of substances with large molecular weights may vary depending on the pore size of the membrane, as in the case of vancomycin. Thus, even if drug dosages can be based on pharmacokinetic studies, selection of a dialysis membrane not studied may cause unpredictable drug concentrations. With these limitations in mind and considering the available literature on pharmacokinetics in patients with renal failure, general guidelines for drug dosage during continuous renal replacement therapy can be given. In haemofiltration, drug protein binding is the major factor determining sieving, i.e. the appearance of the drug in the ultrafiltrate. In haemodialysis, diffusion is added to ultrafiltration, and therefore the saturation of the combined dialysate and ultrafiltrate will decrease further with increasing dialysate flow rate. In continuous haemofiltration or haemodialysis the extracorporeal clearance can be calculated by multiplying the saturation value (estimated or, better, measured) with the ultrafiltrate and dialysate flow rate. Dividing the extracorporeal clearance by the total clearance (including the nonrenal clearance) gives the fraction of the dose removed due to extracorporeal elimination. Whether dosage recommendations available for anuric patients have to be modified or not can be decided on the basis of this value. In case of high nonrenal clearance, the degree of saturation is without clinical significance. Based on these considerations guidelines have been constructed for the effect of extracorporeal elimination on more than 120 different drugs commonly used in intensive care patients.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2005
                August 2005
                18 August 2005
                : 25
                : 4
                : 342-351
                Affiliations
                Department of Nephrology, Pitié-Salpêtrière Hospital, Paris, France
                Article
                86591 Am J Nephrol 2005;25:342–351
                10.1159/000086591
                15980618
                © 2005 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
                Figures: 5, Tables: 3, References: 44, Pages: 10
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/86591
                Categories
                Original Report: Laboratory Investigation

                Cardiovascular Medicine, Nephrology

                Drug removal, Hemodialysis

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