Determination of plasma protein binding of dalbavancin.
J Antimicrob Chemother
; 77(7): 1899-1902, 2022 06 29.
Article
en En
| MEDLINE
| ID: mdl-35488862
ABSTRACT
OBJECTIVES:
Dalbavancin 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.METHODS:
The ultracentrifugation technique was used to determine free dalbavancin concentrations in plasma at two concentrations (50 and 200â mg/L) in duplicate. Centrifuge tubes and pipette tips were treated for 24â 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.RESULTS:
Measurement 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%.CONCLUSIONS:
Dalbavancin 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Infecciones Estafilocócicas
/
Bacteriemia
Límite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos