title: Assessment of oritavancin serum protein binding across species.
abstract: Biophysical methods to study the binding of oritavancin, a lipoglycopeptide, to serum protein are confounded by nonspecific drug adsorption to labware surfaces. We assessed oritavancin binding to serum from mouse, rat, dog, and human by a microbiological growth-based method under conditions that allow near-quantitative drug recovery. Protein binding was similar across species, ranging from 81.9% in human serum to 87.1% in dog serum. These estimates support the translation of oritavancin exposure from nonclinical studies to humans.
authors.affiliation: The Medicines Company, 7170 Frederick-Banting St., 2nd Floor, St. Laurent, Quebec H4S 2A1, Canada. francis.arhin@themedco.com
authors.forename: Francis F
authors.initials: FF
authors.lastname: Arhin
authors.forename: Adam
authors.initials: A
authors.lastname: Belley
authors.forename: Geoffrey
authors.initials: G
authors.lastname: McKay
authors.forename: Sylvain
authors.initials: S
authors.lastname: Beaulieu
authors.forename: Ingrid
authors.initials: I
authors.lastname: Sarmiento
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Parr
authors.forename: Gregory
authors.initials: G
authors.lastname: Moeck
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism*; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology; D017576:Daptomycin / Q000378:metabolism / Q000494:pharmacology; D004285:Dogs; D006020:Glycopeptides / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D000077427:Lipoglycopeptides; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods; D011485:Protein Binding; D051381:Rats; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000187:drug effects; D000097572:Cefpirome; D014640:Vancomycin / Q000031:analogs & derivatives
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D002511:Cephalosporins; D017576:Daptomycin; D006020:Glycopeptides; D000077427:Lipoglycopeptides; D000097572:Cefpirome; C100708:oritavancin; D014640:Vancomycin