title: Pharmacokinetics of dalbavancin in plasma and skin blister fluid.
abstract: OBJECTIVE
  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 AUC(Day 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 beta-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.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT 06102, USA. dnicola@harthosp.org
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
authors.forename: Heather K
authors.initials: HK
authors.lastname: Sun
authors.forename: Elyse
authors.initials: E
authors.lastname: Seltzer
authors.forename: Mary
authors.initials: M
authors.lastname: Buckwalter
authors.forename: James A
authors.initials: JA
authors.lastname: Dowell
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D001768:Blister / Q000139:chemically induced / Q000378:metabolism*; D002193:Cantharidin; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007509:Irritants; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D017334:Teicoplanin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D007509:Irritants; D017334:Teicoplanin; C469289:dalbavancin; D002193:Cantharidin