© 2015 Wichtg Publishing IJAO ISSN 0391-3988 Int J Artf Organs 2015; 38 (8): 419-424 ORIGINAL ARTICLE antbiotc eliminaton (6), and standard dosing for com- monly used antbiotcs in the intensive care unit (ICU) has been shown to frequently be suboptmal among critcally ill patents receiving RRT (7). The clearance of antbiotcs dur- ing RRT is not only caused by RRT-driven solute removal, but potentally also by adsorpton onto the CRRT flter. This phe- nomenon has been shown to be clinically signifcant for some classes of antbiotcs including aminoglycosides (8-11), fuo- roquinolones (12, 13), glycopeptdes, and lipopeptdes (14, 15). Estmatng any additonal clearance by RRT is complex, as there is wide variability in RRT materials, modalites, and setngs. This variability may lead to diferences in antbiotc dosing requirements between patents receiving diferent forms or setngs of RRT, although more data are required to quantfy any pharmacokinetc changes associated with these issues. Numerous clinical pharmacokinetc studies of meropenem and piperacillin in critcally ill patents receiving diferent forms DOI: 10.5301/ijao.5000422 Can we use an ex vivo contnuous hemofltraton model to describe the adsorpton and eliminaton of meropenem and piperacillin? Janatul-Ain Jamal 1 , Andrew A. Udy 2 , Steven C. Wallis 1 , Dwarakanathan Ranganathan 3 , Bret C. McWhinney 4 , Jacobus P.J. Ungerer 4 , Jefrey Lipman 1,5 , Jason A. Roberts 1,5,6 1 Burns, Trauma and Critcal Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland - Australia 2 Department of Hyperbaric and Intensive Care Medicine, The Alfred Hospital, Prahran, Melbourne - Australia 3 Department of Renal Medicine, The Royal Brisbane and Women’s Hospital, Brisbane, Queensland - Australia 4 Department of Chemical Pathology, Pathology Queensland, Brisbane, Queensland - Australia 5 Department of Intensive Care Medicine, The Royal Brisbane and Women’s Hospital, Brisbane, Queensland - Australia 6 Department of Pharmacy, The Royal Brisbane and Women’s Hospital, Brisbane, Queensland - Australia Introducton Commencement of renal replacement therapy (RRT) is common among critcally ill patents (1), and contnuous RRT (CRRT) is the most widely used RRT technique in this popu- laton (2-5). In clinical practce, CRRT can signifcantly afect ABSTRACT Objectves: To determine the adsorpton and eliminaton characteristcs of meropenem and piperacillin during simulated contnuous renal replacement therapy (CRRT), and to compare the observed data from this ex vivo study with previous data from clinical studies. Method: This was an experimental study utlizing a modifed CRRT circuit and polysulfone membrane (1.2 m 2 ), circulated with a blood-crystalloid mixture. Adsorpton onto the CRRT circuit was tested over a 4-h period, and clearance was assessed separately using variable contnuous hemofltraton setngs. Results: A rapid 9% reducton in circulatng meropenem and piperacillin concentratons was observed at ap- proximately 0.5 and 1.0 h for each antbiotc, respectvely. The post-diluton setng was associated with a signif- cantly higher sieving coefcient (Sc) and flter clearance (CL flter ) (mean ± SD) (Sc 1.14 ± 0.10 versus 1.06 ± 0.04; CL flter 19.05 ± 1.63 versus 17.59 ± 0.62 ml/min, P values <0.05) for meropenem. No signifcant diferences were observed for piperacillin pharmacokinetcs. Clinically comparable Sc data were observed between data obtained from the ex vivo study and data from previous clinical studies, for both antbiotcs. Conclusions: Meropenem and piperacillin appear to be rapidly adsorbed into the CRRT circuit, and the delivery site of fuid replacement signifcantly infuences meropenem pharmacokinetcs. However, these fndings are likely to be clinically insignifcant and not afect dosing requirements. This ex vivo method could be a surrogate for future clinical pharmacokinetc studies of CRRT. Further research is required to explore the applicability of the ex vivo method to further characterize antbiotc pharmacokinetcs during CRRT. Keywords: Ex vivo, Renal replacement therapy, Hemofltraton, Pharmacokinetc, Meropenem, Piperacillin Accepted: July 5, 2015 Published online: July 16, 2015 Corresponding author: Ms. Janatul-Ain Jamal Burns Trauma and Critcal Care Research Centre Level 7 Block 6 Royal Brisbane and Women’s Hospital Buterfeld St Brisbane Queensland, 4029 Australia janatulain@gmail.com