Pharmacokinetics of dalbavancin in plasma and skin blister fluid

• Published in: Journal of antimicrobial chemotherapy Vol. 60; no. 3; pp. 681 - 684
• Main Authors: Nicolau, David P., Sun, Heather K., Seltzer, Elyse, Buckwalter, Mary, Dowell, James A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2007; Oxford Publishing Limited (England)
• Subjects: Adult; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Area Under Curve; Bacteria; Biological and medical sciences; Biotransformation; Blister - chemically induced; Blister - metabolism; Body fluids; Bullous diseases of the skin; Cantharidin; Chromatography, High Pressure Liquid; cSSSIs; Dermatology; Female; Humans; Infections; Infusions, Intravenous; Irritants; Kinetics; lipoglycopeptides; Male; Medical sciences; Middle Aged; Pharmacology; Pharmacology. Drug treatments; Plasma - chemistry; Skin - metabolism; Staphylococcus aureus; Tandem Mass Spectrometry; Teicoplanin - adverse effects; Teicoplanin - analogs & derivatives; Teicoplanin - blood; Teicoplanin - pharmacokinetics; lipoglycopeptides; infections; cSSSIs; Bullous dermatosis; Biological fluid; Skin disease; Skin bulla; Peptides; Blood plasma; Infection; Antibiotic; Glycopeptide; Dalbavancin; Antibacterial agent; Pharmacokinetics
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkm263

Objectives Dalbavancin is a novel lipoglycopeptide antibiotic in development for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria. The aim of the present study was to assess the penetration of dalbavancin into skin blister fluid. Methods Nine healthy subjects (five males; ranging in age from 26 to 57 years) were administered a single 30 min intravenous infusion of dalbavancin at a dose of 1000 mg. Skin blisters were induced by application of cantharidin ointment. Plasma and blister fluid samples were collected over 7 days post-dose, and concentrations of dalbavancin were assessed by a validated LC/MS/MS assay. Pharmacokinetics were determined by non-compartmental methods, and drug penetration was assessed based on the ratio of area under the curve (AUC) in the blister fluid versus plasma for each subject. Results The mean (SD) peak concentration of dalbavancin in plasma and blister fluid was 285 (31.1) and 67.3 (18.2) mg/L, respectively; the corresponding AUCDay 7 values were 10 806 (1926) and 6438 (1238) mg · h/L, respectively. The mean (SD) penetration of dalbavancin into blister fluid was 59.6% (6.3%). By Day 7, the mean concentration of dalbavancin in plasma and blister fluid was 46.5 and 30.3 mg/L, respectively. Conclusions Dalbavancin concentrations in blister fluid remained well above the MIC90 values for pathogens commonly implicated in cSSSIs such as Staphylococcus aureus, including methicillin-resistant S. aureus (MIC90 = 0.06 mg/L) and β-haemolytic streptococci (MIC90 = 0.03 mg/L) through Day 7. These pharmacokinetic data support the use of dalbavancin in the treatment of cSSSIs caused by susceptible Gram-positive pathogens.