title: Doripenem Treatment during Continuous Renal Replacement Therapy.
abstract: Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against Pseudomonas aeruginosa. While the initial dosing recommendation for renally competent patients and patients undergoing continuous renal replacement therapy (cRRT) was 500 mg every 8 h (q8h), the dose for renally competent patients was updated to 1 g q8h in June 2012. There are no updated data for the dosing of patients on continuous renal replacement therapy. The original dosing regimen for cRRT patients was based on nonseptic patients, while newer publications chose comparatively low target concentrations for a carbapenem. Thus, there is an urgent need for updated recommendations for dosing during cRRT. In the trial presented here, we included 13 oliguric septic patients undergoing cRRT in an intensive care setting. Five patients each were treated with hemodiafiltration or hemodialysis, while three patients received hemofiltration treatment. All patients received 1 g doripenem every 8 h. Doripenem concentrations in the plasma and ultrafiltrate were measured over 48 h. The mean hemofilter clearance was 36.53 ml/min, and the mean volume of distribution was 59.26 liters. The steady-state trough levels were found at 8.5 mg/liter, with no considerable accumulation. Based on pharmacokinetic and pharmacodynamic considerations, we propose a regimen of 1 g q8h, which may be combined with a loading dose of 1.5 to 2 g for critically ill patients. (This study has been registered with EudraCT under registration no. 2009-018010-18 and at ClinicalTrials.gov under registration no. NCT02018939.).
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria matthias.vossen@meduniwien.ac.at.
authors.forename: M G
authors.initials: MG
authors.lastname: Vossen
authors.affiliation: Department of Hospital Hygiene, Wilhelminenspital, Vienna, Austria.
authors.forename: J M
authors.initials: JM
authors.lastname: Wenisch
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Maier-Salamon
authors.affiliation: Institute of Pharmacy, Clinical Pharmacy, University of Bonn, Bonn, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Fritsch
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Saria
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Zuba
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Jilch
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Lemmerer
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Unger
authors.affiliation: Institute of Pharmacy, Clinical Pharmacy, University of Bonn, Bonn, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Jaehde
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Jäger
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Thalhammer
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015780:Carbapenems / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003422:Critical Care; D000077726:Doripenem; D005260:Female; D017583:Hemodiafiltration; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D006435:Renal Dialysis
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem