Elimination of doripenem during dialysis and pharmacokinetic evaluation of post-hemodialytic dosing in intermittent renal replacement therapy [PublishAheadOfPrint]

Objectives: Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against Pseudomonas aeruginosa and Enterobacteriaceae. Current dosing regimens recommend the administration of 0.25-0.5 g once daily in patients undergoing intermittent renal replacement therapy. As patients are usually dialyzed thrice weekly, we aimed to investigate a 1-g post-hemodialysis regimen, thus reducing treatment costs and enhancing patient compliance. A second objective of this trial was to describe the pharmacokinetics of intradialytic doripenem.

Patients: Ten oliguric or anuric patients in need of intermittent renal replacement therapy were included in this trial. All patients suffered from a septic episode.

Results: The mean hemofilter clearance was 123.46 ± 42.03 ml/min, and the total body clearance in between hemodialysis sessions was 16.79 ± 6.02 ml/min. The average pre-hemodialysis trough concentration was 2.4 ± 1.3 mg/l, while the EUCAST resistance breakpoint for Enterobacteriaceae is set at 2 mg/l. The interpatient variability was considerably higher than the intrapatient variability. Apart from one patient who suffered an allergic reaction, doripenem was tolerated well by all patients.

Conclusion: Our data indicate, that post-hemodialysis administration of 1 g doripenem result in sufficient plasma levels in anuric, but not oliguric patients during the entire dosing interval.

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