Can we use an ex vivo continuous hemofiltration model to describe the adsorption and elimination of meropenem and piperacillin?

Janattul Ain Jamal, Andrew A. Udy, Steven C. Wallis, Dwarakanathan Ranganathan, Brett C. McWhinney, Jacobus P J Ungerer, Jeffrey Lipman, Jason A. Roberts

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Objectives: 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. Method: 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, andclearance 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.

Original languageEnglish
Pages (from-to)419-424
Number of pages6
JournalInternational Journal of Artificial Organs
Volume38
Issue number8
DOIs
Publication statusPublished - Aug 2015
Externally publishedYes

Keywords

  • Ex vivo
  • Hemofiltration
  • Meropenem
  • Pharmacokinetic
  • Piperacillin
  • Renal replacement therapy

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