Can we use an ex vivo continuous hemofiltration model to describe the adsorption and elimination of meropenem and piperacillin?
OBJECTIVE
To determine the adsorption and elimination characteristics of meropenem and piperacillin during simulated continuous renal replacement therapy (CRRT), and to compare the observed data from this ex vivo study with previous data from clinical studies.


METHODS
This was an experimental study utilizing a modified CRRT circuit and polysulfone membrane (1.2 m2), circulated with a blood-crystalloid mixture. Adsorption onto the CRRT circuit was tested over a 4-h period, and clearance was assessed separately using variable continuous hemofiltration settings.


RESULTS
A rapid 9% reduction in circulating meropenem and piperacillin concentrations was observed at approximately 0.5 and 1.0 h for each antibiotic, respectively. The post-dilution setting was associated with a significantly higher sieving coefficient (Sc) and filter clearance (CLfilter) (mean ± SD) (Sc 1.14 ± 0.10 versus 1.06 ± 0.04; CLfilter 19.05 ± 1.63 versus 17.59 ± 0.62 ml/min, P values < 0.05) for meropenem. No significant differences were observed for piperacillin pharmacokinetics. Clinically comparable Sc data were observed between data obtained from the ex vivo study and data from previous clinical studies, for both antibiotics.


CONCLUSIONS
Meropenem and piperacillin appear to be rapidly adsorbed into the CRRT circuit, and the delivery site of fluid replacement significantly influences meropenem pharmacokinetics. However, these findings are likely to be clinically insignificant and not affect dosing requirements. This ex vivo method could be a surrogate for future clinical pharmacokinetic studies of CRRT. Further research is required to explore the applicability of the ex vivo method to further characterize antibiotic pharmacokinetics during CRRT.
Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland - Australia.
Janattul-Ain
JA
Jamal
Department of Hyperbaric and Intensive Care Medicine, The Alfred Hospital, Prahran, Melbourne - Australia.
Andrew A
AA
Udy
Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland - Australia.
Steven C
SC
Wallis
Department of Renal Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland - Australia.
Dwarakanathan
D
Ranganathan
Department of Chemical Pathology, Pathology Queensland, Brisbane, Queensland - Australia.
Brett C
BC
McWhinney
Department of Chemical Pathology, Pathology Queensland, Brisbane, Queensland - Australia.
Jacobus P J
JP
Ungerer
Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland - Australia.|Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland - Australia.
Jeffrey
J
Lipman
Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland - Australia.|Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland - Australia.|Department of Pharmacy, The Royal Brisbane and Women's Hospital, Brisbane, Queensland - Australia.
Jason A
JA
Roberts
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D006440:Hemofiltration; D006801:Humans; D000077731:Meropenem; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D015233:Models, Statistical; D013845:Thienamycins / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem