Elimination of Doripenem during Dialysis and Pharmacokinetic Evaluation of Posthemodialysis Dosing for Patients Undergoing Intermittent Renal Replacement Therapy

Abstract

Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against and Current dosing regimens recommend the administration of 0.25 to 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 posthemodialysis regimen, thus reducing treatment costs and enhancing patient compliance. A second objective of this trial was to describe the pharmacokinetics of intradialytic doripenem. Ten oliguric or anuric patients in need of intermittent renal replacement therapy were included in this trial. All patients suffered from a septic episode. The mean hemofilter clearance was 123.46 ± 42.03 ml/min, and the total body clearance between hemodialysis sessions was 16.79 ± 6.02 ml/min. The average prehemodialysis trough concentration was 2.4 ± 1.3 mg/liter, while the EUCAST resistance breakpoint for is set at 2 mg/liter. 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. Our data indicate that posthemodialysis administration of 1 g of doripenem results in sufficient plasma levels in anuric but not oliguric patients during the entire dosing interval. (This trial was registered with EudraCT under registration no. 2009-018010-18 and at ClinicalTrials.gov under registration no. NCT02018939.).

In vitro Evaluation of Linezolid and Doripenem Clearance with Different Hemofilters

“…Since the protein nonbinding rate of dripenem is 0.91, a calculated SC value of 0.91 represents the free doripenem filtered without being adsorbed on membranes [18]. Our results were similar, suggesting that doripenem was not adsorbed on AN69ST, PMMA, or PS membranes [6].…”

“…Especially in severe sepsis and septic shock are major causes of morbidity and mortality in the ICUs, applicable international guidelines early recommend the early use of carbapenems as empirical therapy [5]. Owing to their hydrophilicity, they are readily removed by hemofilters during RRT for septic AKI [6,7]. Appropriate antibiotic therapy during RRT is critical because it affects both the patients' prognosis and the emergence of resistant bacteria.…”

In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model

“…Serum and ultrafiltrate concentration of the investigated drug was measured by high performance liquid chromatography at the Department of Pharmaceutical Sciences at the University of Vienna, Austria (doripenem, described in ( Vossen et al, 2018 ) ) or by CE certified assay based on kinetic interaction of microparticles in a solution using a Cobas c501 device at the Department of Laboratory Medicine of the General Hospital of Vienna, Austria (Cobas GENT2 Online TDM Gentamicin, Cobas VANC3 Online TDM Vancomycin Gen.3 (Roche Diagnostics GmbH), QMS Teicoplanin (Microgenetics Corporation, Thermo Fisher Scientific Inc.).…”

Therapeutic Drug Monitoring of Antibiotic Drugs in Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis: A Critical Review

“…Vossen et al documented that 70% of patients undergoing IHD/IHDF exhibited Cmin of .2 mg/L at a daily dose of 13.3 mg/kg and 1 g postdialytic additional dose. 40,63 Overexposure has also been reported. Although the MIC-based definition of overexposure is debatable, Donnellan et al 37 reported that 83% and 17% of patients displayed a meropenem trough concentration of .10 MIC, with MICs of 2 and 8 mg/L, respectively.…”