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      How to Calculate Clearance of Highly Protein-Bound Drugs during Continuous Venovenous Hemofiltration Demonstrated with Flucloxacillin

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          Abstract

          Background: Flucloxacillin is an important antimicrobial drug in the treatment of infections with Staphylococcus aureus and therefore is often used in staphylococcal infections. Furthermore, flucloxacillin has a high protein binding rate as for example ceftriaxone or teicoplanin – drugs which have formerly been characterized as not being dialyzable. Methods: The pharmacokinetic parameters of 4.0 g flucloxacillin every 8 h were examined in 10 intensive care patients during continuous venovenous hemofiltration (CVVH) using a polyamide capillary hemofilter. In addition, the difficulty of calculating the hemofiltration clearance of a highly protein-bound drug is described. Results: Flucloxacillin serum levels were significantly lowered (56.9 ± 24.0%) even though only 15% of the drug was detected in the ultrafiltrate. Elimination half-life, total body clearance and sieving coefficient were 4.9 ± 0.7 h, 117.2 ± 79.1 ml/min and 0.21 ± 0.09, respectively. These discrepancies can be explained by the high protein binding of flucloxacillin, the adsorbing property of polyamide and the equation in order to calculate hemofiltration clearance. The unbound fraction of a 4.0 g flucloxacillin dosage facilitates time above the minimum inhibitory concentration (T > MIC) of 60% only for strains up to a minimum inhibitory concentration (MIC) of 0.5 mg/l. Conclusion: Based on the data of this study, we conclude that intensive care patients with staphylococcal infections on CVVH should be treated with 4.0 g flucloxacillin every 8 h which was safe and well tolerated. Moreover, further studies with highly protein-bound drugs are recommended to check the classical ‘hemodialysis’ equation as the standard equation in calculating the CVVH clearance of highly protein-bound drugs.

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          Therapeutic Drug Monitoring–Guided High Teicoplanin Dosage Regimen Required to Treat a Hypoalbuminemic Renal Transplant Patient Undergoing Continuous Venovenous Hemofiltration

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            Continuous Renal Replacement Therapy in Acute Renal Failure

             Werner Riegel (2003)
            The management of acute renal failure in the critically ill patient is extremely variable and there are no published standards for the provision of renal replacement therapy in this population. Continuous renal replacement therapy seems to be the treatment of choice because of its superior metabolic and hemodynamic control. There is better organ protection by continuous treatment but no evidence for better survival or renal recovery due to continuous treatment. The debate about optimal membrane as well as about optimal dialysis dose is ongoing. An effluent flow rate of at least 35 ml/kg/h as well as lower BUN level at treatment initiation seem to be necessary to provide better survival rate. Peritoneal dialysis is a less suitable option in continuous renal replacement of the adult intensive care patient but hybrid methods such as extended daily dialysis and sustained low efficient daily dialysis need consideration with respect to continuous hemofiltration/dialysis.
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              Author and article information

              Journal
              KBR
              Kidney Blood Press Res
              10.1159/issn.1420-4096
              Kidney and Blood Pressure Research
              S. Karger AG
              978-3-8055-7600-0
              978-3-318-00991-0
              1420-4096
              1423-0143
              2003
              2003
              05 June 2003
              : 26
              : 2
              : 135-140
              Affiliations
              aDepartment of Internal Medicine I, Division of Infectious Diseases, bDepartment of Internal Medicine I, Intensive Care Unit, cDepartment of Internal Medicine II, Division of Cardiology, and dInstitute of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria
              Article
              70997 Kidney Blood Press Res 2003;26:135–140
              10.1159/000070997
              12771540
              © 2003 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: 1, Tables: 2, References: 19, Pages: 6
              Product
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/70997
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