Daptomycin elimination by CVVH in vitro: evaluation of factors influencing sieving and membrane adsorption.
OBJECTIVE
Knowledge on the elimination of antibiotics by extracorporeal hemofiltration is a prerequisite for appropriate antimicrobial dosing in patients with renal failure. The present study set out to determine the clearance of the novel lipopetide antibiotic daptomycin from human whole blood by continuous venovenous hemofiltration (CVVH) in vitro. In addition, factors influencing daptomycin sieving and membrane adsorption were investigated.


METHODS
A recirculation model using different solvent media was established and daptomycin was added to the simulated blood circuit at varying concentrations. The concentration of daptomycin over time in the modelled blood compartment and the ultrafiltrate was measured by high performance liquid chromatography (HPLC).


RESULTS
Mean Sieving coefficients (SCs) of daptomycin over time were calculated to 0.98 +/- 0.05, 0.33 +/- 0.02 and 0.40 +/- 0.03 at a baseline concentration of 60 microg/ml in Ringer lactate, Ringer lactate containing human albumin and in human whole blood, respectively. SCs of daptomycin in protein-containing media were higher than the free fraction in plasma of approximately 10%. Neither concentration of daptomycin nor addition of a second antibiotic showed significant impact on the SC. Adsorption of daptomycin to synthetic surfaces proved moderate and saturable, resulting in loss of around 20% of the amount initially added to the artificial blood circuit.


CONCLUSIONS
In our in vitro setting the calculated clearance of daptomycin from whole blood exceeded the physiological clearance described for individuals with normal renal function. Investigation of clearance by CVVH in vivo seems necessary. Until sufficient clinical data are available for patients undergoing CVVH, monitoring of daptomycin concentrations in this population might be recommended in order to avoid sub-therapeutic exposure to daptomycin.
Wagner
C C
CC
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Steiner
I
I
Zeitlinger
M
M
D000327:Adsorption; D000900:Anti-Bacterial Agents / Q000097:blood / Q000494:pharmacology*; D002511:Cephalosporins / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D017576:Daptomycin / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006440:Hemofiltration; D006801:Humans; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D012212:Rheology; D000097572:Cefpirome
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D017576:Daptomycin; D008567:Membranes, Artificial; D000097572:Cefpirome