Daptomycin elimination by continuous venovenous hemofiltration: in vitro evaluation of factors...

1
BioMed Central Page 1 of 1 (page number not for citation purposes) BMC Pharmacology Open Access Meeting abstract Daptomycin elimination by continuous venovenous hemofiltration: in vitro evaluation of factors influencing sieving and membrane adsorption Claudia Wagner 1 , Ilka Steiner 2 and Markus Zeitlinger* 1 Address: 1 Department of Clinical Pharmacology, Medical University of Vienna, Austria and 2 Institute of Pharmacology, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Austria Email: Markus Zeitlinger* - [email protected] * Corresponding author The present in vitro study set out to determine for the first time the continuous venovenous hemofiltration (CVVH) clearance of the novel lipopetide antibiotic, daptomycin, from human whole blood. Factors influencing daptomy- cin sieving and membrane adsorption were investigated in an in vitro setting. A recirculation model was estab- lished and daptomycin was added to the simulated blood circuit at different concentrations and in different solvent systems. The concentration of daptomycin over time in the modelled blood compartment and in ultrafiltrate was measured by HPLC. Mean sieving coefficients (SCs) of daptomycin over time were 1 ± 0.05, 0.3 ± 0.02 and 0.4 ± 0.03 in Ringer lactate, Ringer lactate containing human albumin and plasma, respectively. The CVVH clearance of daptomycin from whole blood exceeded the physiologi- cal clearance in an individual with normal renal function. Adsorption of daptomycin to synthetic surfaces proved moderate, resulting in loss of around 20% of the initial dose at 1 hour after the start of CVVH. Since mean SCs of daptomycin in protein-containing media were higher than the free fraction in plasma, our results suggest that besides protein binding, unknown factors such as intrac- ellular drug partitioning influence sieving of daptomycin during hemofiltration. Due to the high in vitro CVVH clearance of daptomycin we determined from human whole blood, we recommend monitoring of daptomycin concentrations in patients undergoing hemofiltration. from 13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT) Vienna, Austria. 22–24 November 2007 Published: 14 November 2007 BMC Pharmacology 2007, 7(Suppl 2):A21 doi:10.1186/1471-2210-7-S2-A21 <supplement> <title> <p>13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT)</p> </title> <editor>Ernst Singer and Thomas Griesbacher</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="[http://www.biomedcentral.com/content/files/pdf/1471-2210-7-S2-full.pdf]">here</a></note> <url>http://www.biomedcentral.com/content/pdf/1471-2210-7-S2-info.pdf</url> </supplement> This abstract is available from: http://www.biomedcentral.com/1471-2210/7/S2/A21 © 2007 Wagner et al; licensee BioMed Central Ltd.

Transcript of Daptomycin elimination by continuous venovenous hemofiltration: in vitro evaluation of factors...

Page 1: Daptomycin elimination by continuous venovenous hemofiltration: in vitro evaluation of factors influencing sieving and membrane adsorption

BioMed Central

Page 1 of 1(page number not for citation purposes)

BMC Pharmacology

Open AccessMeeting abstractDaptomycin elimination by continuous venovenous hemofiltration: in vitro evaluation of factors influencing sieving and membrane adsorptionClaudia Wagner1, Ilka Steiner2 and Markus Zeitlinger*1

Address: 1Department of Clinical Pharmacology, Medical University of Vienna, Austria and 2Institute of Pharmacology, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Austria

Email: Markus Zeitlinger* - [email protected]

* Corresponding author

The present in vitro study set out to determine for the firsttime the continuous venovenous hemofiltration (CVVH)clearance of the novel lipopetide antibiotic, daptomycin,from human whole blood. Factors influencing daptomy-cin sieving and membrane adsorption were investigatedin an in vitro setting. A recirculation model was estab-lished and daptomycin was added to the simulated bloodcircuit at different concentrations and in different solventsystems. The concentration of daptomycin over time inthe modelled blood compartment and in ultrafiltrate wasmeasured by HPLC. Mean sieving coefficients (SCs) ofdaptomycin over time were 1 ± 0.05, 0.3 ± 0.02 and 0.4 ±0.03 in Ringer lactate, Ringer lactate containing humanalbumin and plasma, respectively. The CVVH clearance ofdaptomycin from whole blood exceeded the physiologi-cal clearance in an individual with normal renal function.Adsorption of daptomycin to synthetic surfaces provedmoderate, resulting in loss of around 20% of the initialdose at 1 hour after the start of CVVH. Since mean SCs ofdaptomycin in protein-containing media were higherthan the free fraction in plasma, our results suggest thatbesides protein binding, unknown factors such as intrac-ellular drug partitioning influence sieving of daptomycinduring hemofiltration. Due to the high in vitro CVVHclearance of daptomycin we determined from humanwhole blood, we recommend monitoring of daptomycinconcentrations in patients undergoing hemofiltration.

from 13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT)Vienna, Austria. 22–24 November 2007

Published: 14 November 2007

BMC Pharmacology 2007, 7(Suppl 2):A21 doi:10.1186/1471-2210-7-S2-A21

<supplement> <title> <p>13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT)</p> </title> <editor>Ernst Singer and Thomas Griesbacher</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="[http://www.biomedcentral.com/content/files/pdf/1471-2210-7-S2-full.pdf]">here</a></note> <url>http://www.biomedcentral.com/content/pdf/1471-2210-7-S2-info.pdf</url> </supplement>

This abstract is available from: http://www.biomedcentral.com/1471-2210/7/S2/A21

© 2007 Wagner et al; licensee BioMed Central Ltd.