Pharmacokinetics of doripenem during high volume hemodiafiltration in patients with septic shock. (30th December 2014)

• Record Type: Journal Article
• Authors: Tamme, Kadri; Oselin, Kersti; Kipper, Karin; Low, Kaywei; Standing, Joseph F.; Metsvaht, Tuuli; Karjagin, Juri; Herodes, Koit; Kern, Hartmut; Starkopf, Joel
• Is Part Of: Journal of clinical pharmacology. Volume 55:Number 4(2015:Apr.)
• Page Start: 438
• Page End: 446
• Publication Date: 2014-12-30
• Subjects: Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.432
• Languages: English
• ISSNs: 0091-2700

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jcph432-sec-0001" sec-type="section"> <p>Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (12 samples) after study drug administration. Doripenem concentrations were determined by ultrahigh performance liquid chromatography‐tandem mass spectrometry. Population PK analysis and Monte Carlo simulation of 1, 000 subjects were performed. The median convective volume of HVHDF was 10.3 L/h and urine output during the sampling period was 70 mL. The population mean total doripenem clearance on HVHDF was 6.82 L/h, volume of distribution of central compartment 10.8 L, and of peripheral compartment 12.1 L. Doses of 500 mg every 8 hours resulted in 88.5% probability of attaining the target of 50% time over MIC for bacteria with MIC = 2 µg/mL at 48 hours, when doubling of MIC during that time was assumed. Significant elimination of doripenem occurs during HVHDF. Doses of 500 mg every 8 hours are necessary for treatment of infections caused by susceptible bacteria during extended HVHDF.</p> </sec> </abstract>