title: In vitro characterization of oritavancin clearance from human blood by low-flux, high-flux, and continuous renal replacement therapy dialyzers.
abstract: BACKGROUND
  Oritavancin is an investigational lipoglycopeptide antibiotic under clinical development for the treatment of gram-positive bacterial infections. The impact of hemodialysis on plasma concentrations of oritavancin is unknown and may be important in making dosage adjustments in such patients. The present study sought to determine the clearance of oritavancin from human blood by various commercially available dialyzers in an in vitro hemodialysis model.
  
  
  METHODS
  Three types each of low-flux (Dicea 130, F6, and Polyflux 14L) and high-flux (Revaclear, Exeltra 150, and Optiflux F160NR) dialyzers and one type of continuous renal replacement therapy (CRRT) dialyzer (Prismaflex M100) were studied. Heparinized human blood containing oritavancin (200 mg/L) was circulated from a reservoir to the dialyzers and back to the reservoir. Fresh dialysate was pumped through the dialyzers in a countercurrent manner. Blood samples from each side of the dialyzers and contaminated dialysate samples were collected at periodic intervals. Oritavancin levels were analyzed by a liquid chromatography/mass spectrometry method with a limit of quantification of 12.5 ng/mL and plasma clearances of oritavancin were calculated.
  
  
  RESULTS
  The mean dialytic clearance of oritavancin was insignificant for each of the low-flux, high-flux and CRRT dialyzers. Clinically significant amounts of oritavancin were not detected in dialysate during any of the experimental dialysis sessions.
  
  
  CONCLUSIONS
  The clearance of oritavancin from human blood by the dialyzers used in this study is insignificant. Further clinical studies would be required before making changes in dosage of oritavancin in hemodialysis patients.
authors.affiliation: College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. kuma0070@umn.edu
authors.forename: Atul
authors.initials: A
authors.lastname: Kumar
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Mann
authors.forename: Mani
authors.initials: M
authors.lastname: Keshtgarpour
authors.forename: Michael A
authors.initials: MA
authors.lastname: Flynn
authors.forename: Hong
authors.initials: H
authors.lastname: Deng
authors.forename: Adel Rafai
authors.initials: AR
authors.lastname: Far
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Parr
authors.forename: Susan R
authors.initials: SR
authors.lastname: Moriarty
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D015314:Dialysis Solutions / Q000737:chemistry; D004867:Equipment Design; D006020:Glycopeptides / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D000077427:Lipoglycopeptides; D013058:Mass Spectrometry; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011485:Protein Binding; D006435:Renal Dialysis / Q000295:instrumentation*; D014640:Vancomycin / Q000031:analogs & derivatives
chemical_list: D000900:Anti-Bacterial Agents; D015314:Dialysis Solutions; D006020:Glycopeptides; D000077427:Lipoglycopeptides; C100708:oritavancin; D014640:Vancomycin