In vitro Characterization of Oritavancin Clearance from Human Blood by Low-Flux, High-Flux, and Continuous Renal Replacement Therapy Dialyzers

• Published in: International journal of artificial organs Vol. 34; no. 11; pp. 1067 - 1074
• Main Authors: Kumar, Atul, Mann, Henry J., Keshtgarpour, Mani, Flynn, Michael A., Deng, Hong, Far, Adel Rafai, Parr, Thomas R., Moriarty, Susan R.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-11-2011; Wichtig
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Chromatography, Liquid; Dialysis Solutions - chemistry; Emergency and intensive care: renal failure. Dialysis management; Equipment Design; Glycopeptides - blood; Glycopeptides - pharmacokinetics; Humans; Intensive care medicine; Mass Spectrometry; Medical sciences; Metabolic Clearance Rate; Models, Biological; Pharmacology. Drug treatments; Protein Binding; Renal Dialysis - instrumentation; In vitro model; Clearance; Oritavancin; Pharmacokinetics; Hemodialysis; CRRT; High; Human; Peptides; Continuous; Flux; In vitro; Blood; Characterization; Dialyzer; Extrarenal dialysis; Glycopeptide; Models; Antibacterial agent
• ISSN: 0391-3988; 1724-6040
• DOI: 10.5301/ijao.5000008

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.