Determination of plasma protein binding of dalbavancin.
| dc.contributor.author | Turner, Nicholas A | |
| dc.contributor.author | Xu, Allan | |
| dc.contributor.author | Zaharoff, Smitha | |
| dc.contributor.author | Holland, Thomas L | |
| dc.contributor.author | Lodise, Thomas P | |
| dc.date.accessioned | 2024-01-01T21:01:35Z | |
| dc.date.available | 2024-01-01T21:01:35Z | |
| dc.date.issued | 2022-06 | |
| dc.description.abstract | ObjectivesDalbavancin is a lipoglycopeptide with a long half-life, making it a promising treatment for infections requiring prolonged therapy, such as complicated Staphylococcus aureus bacteraemia. Free drug concentration is a critical consideration with prolonged treatment, since free concentration-time profiles may best correlate with therapeutic effect. In support of future clinical trials, we aimed to develop a reliable and reproducible assay for measuring free dalbavancin concentrations.MethodsThe ultracentrifugation technique was used to determine free dalbavancin concentrations in plasma at two concentrations (50 and 200 mg/L) in duplicate. Centrifuge tubes and pipette tips were treated for 24 h before use with Tween 80 to assess adsorption. Dalbavancin concentrations were analysed from the plasma samples (total) and middle layer samples (free) by LC/MS/MS with isotopically labelled internal standard. Warfarin served as a positive control with known high protein binding.ResultsMeasurement of free dalbavancin was sensitive to adsorption onto plastic. Treatment of tubes and pipette tips with ≥2% Tween 80 effectively prevented drug loss during protein binding experiments. By the ultracentrifugation method, dalbavancin's protein binding was estimated to be approximately 99%.ConclusionsDalbavancin has very high protein binding. Given dalbavancin's high protein binding, accurate measurement of free dalbavancin concentrations should be a key consideration in future exposure-response studies, especially clinical trials. Future investigations should confirm if the active fraction is best predicted by the free or total fraction. | |
| dc.identifier | 6576321 | |
| dc.identifier.issn | 0305-7453 | |
| dc.identifier.issn | 1460-2091 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Oxford University Press (OUP) | |
| dc.relation.ispartof | The Journal of antimicrobial chemotherapy | |
| dc.relation.isversionof | 10.1093/jac/dkac131 | |
| dc.rights.uri | ||
| dc.subject | Humans | |
| dc.subject | Staphylococcus aureus | |
| dc.subject | Bacteremia | |
| dc.subject | Staphylococcal Infections | |
| dc.subject | Polysorbates | |
| dc.subject | Teicoplanin | |
| dc.subject | Anti-Bacterial Agents | |
| dc.subject | Microbial Sensitivity Tests | |
| dc.subject | Protein Binding | |
| dc.subject | Tandem Mass Spectrometry | |
| dc.title | Determination of plasma protein binding of dalbavancin. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Turner, Nicholas A|0000-0003-0650-4894 | |
| duke.contributor.orcid | Holland, Thomas L|0000-0001-7745-9010 | |
| pubs.begin-page | 1899 | |
| pubs.end-page | 1902 | |
| pubs.issue | 7 | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Medicine | |
| pubs.organisational-group | Medicine, Infectious Diseases | |
| pubs.organisational-group | Duke Clinical Research Institute | |
| pubs.publication-status | Published | |
| pubs.volume | 77 |
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