Abstract
BackgroundThe purpose of this study was to evaluate the feasibility of utilizing an in-vitro, closed loop hemodialysis system as a method to assess drug clearance. Secondarily, this study tested the influence of variables (blood flow rate, dialysate flow rate, and type of filter) in the hemodialysis procedure on the clearance of vancomycin and gentamicin.MethodsAn in-vitro, closed loop hemodialysis system was constructed. The vancomycin (30 mg/L) and gentamicin (25 mg/L) were added to a simulated blood system (SBS). Four conditions (C1-C4) were tested by defining the filter (Polyflux 170H or F180) and the blood and dialysate flow rates (BFR and DFR). All hemodialysis sessions were 3 hours in length and each condition was completed in duplicate. Dialysate effluent was collected in a 50 gallon polyethylene drum. Samples were collected (in duplicate) from the SBS and the dialysate effluent at baseline and at the end of the hemodialysis session. Samples were analyzed for vancomycin and gentamicin with an ultrahigh performance liquid chromatography/tandem mass spectrometry method.ResultsA total of eight 3-hour hemodialysis sessions were conducted. For all tested conditions (C1-C4), vancomycin was undetectable in the SBS at the end of dialysis. However, total vancomycin recovery in the dialysis effluent was 85±18%, suggesting that up to 15% may have adsorbed to the dialysis filter or tubing. Gentamicin clearance from SBS was >98% in all tested conditions. Average gentamicin recovery in the dialysate effluent was 99±15%.ConclusionBoth vancomycin and gentamicin were readily removed by high-flux hemodialysis under all conditions studied. No significant differences in drug clearance were observed between conditions used in this in vitro study. The clinical implications of changing these hemodialysis parameters are unknown.
Highlights
The purpose of this study was to evaluate the feasibility of utilizing an in-vitro, closed loop hemodialysis system as a method to assess drug clearance
Vancomycin and gentamicin clearances were similar in Condition 1 (C1) (BFR 400 mL/min and dialysate flow rates (DFR) 600 mL/min) and Condition 2 (C2) (BFR 500 and DFR 800 ml/min) in Optiflux filter
Regardless of types of filter, the rate of Blood flow rate (BFR) and DFR, vancomycin was undetectable in the simulated blood system (SBS) at the end of dialysis for all tested conditions (C1-Condition 4 (C4)), suggesting the drug is readily cleared by contemporary hemodialysis
Summary
The purpose of this study was to evaluate the feasibility of utilizing an in-vitro, closed loop hemodialysis system as a method to assess drug clearance. This study tested the influence of variables (blood flow rate, dialysate flow rate, and type of filter) in the hemodialysis procedure on the clearance of vancomycin and gentamicin. Pharmacokinetics are significantly altered during hemodialysis and require directed studies in this setting in order to guide drug dosing [1,2]. These clinical studies provide valuable information but are limited since dialysis variables (flow rates, filter selection, time on dialysis) may or may not be standardized [3-11]. This study was aimed at characterizing the clearance of vancomycin and gentamicin and the influence of changes in 3 variables (BFR, DFR and hemodialysis filters) on clearance in a closed loop in vitro dialysis system. It is hypothesized that the clearance of vancomycin and gentamicin will increase with increasing flow rates and more efficient hemodialysis filters
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have