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.
MeSH terms
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Animals
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Anti-Bacterial Agents / metabolism*
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Anti-Bacterial Agents / pharmacology
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Blood Proteins / metabolism*
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Cefpirome
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Cephalosporins / metabolism
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Cephalosporins / pharmacology
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Daptomycin / metabolism
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Daptomycin / pharmacology
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Dogs
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Glycopeptides / metabolism*
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Glycopeptides / pharmacology
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Humans
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Lipoglycopeptides
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Mice
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Microbial Sensitivity Tests / methods
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Protein Binding
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Rats
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Species Specificity
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Staphylococcus aureus / drug effects
Substances
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Anti-Bacterial Agents
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Blood Proteins
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Cephalosporins
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Glycopeptides
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Lipoglycopeptides
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Daptomycin
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oritavancin