title: Dalbavancin Pharmacokinetics and Safety in Children 3 Months to 11 Years of Age.
abstract: Dalbavancin is a novel lipoglycopeptide antibiotic that has potent in vitro activity against Gram-positive microorganisms.
  
  
  
  We performed a phase 1, open-label, multicenter study to investigate the pharmacokinetics (PK) and safety of a single dose of intravenous dalbavancin in hospitalized pediatric subjects 3 months to 11 years of age. We combined these data with previously collected adolescent PK data and performed a population PK analysis.
  
  
  
  Model development was performed using 311 dalbavancin plasma concentrations from 43 subjects. The median age was 5.9 years (range: 0.3-16.9). A 3-compartment, linear PK model was developed. Based on simulations, the following age-dependent dosing regimen was found to achieve similar dalbavancin exposure to that in adults administered a 2-dose regimen: children 6 to <18 years of age, 12 mg/kg (1000 mg maximum) on day 1 and 6 mg/kg (500 mg maximum) on day 8 and children 3 months to <6 years of age, 15 mg/kg (1000 mg maximum) on day 1 and 7.5 mg/kg (500 mg maximum) on day 8. Similarly, the following age-dependent regimen was found to match adult exposure after a single-dose (1500 mg): 6 to <18 years of age, 18 mg/kg (1500 mg maximum) on day 1 and 3 months to <6 years of age, 22.5 mg/kg (1500 mg maximum) on day 1. Nineteen subjects experienced 36 treatment-emergent adverse events. Five of 36 adverse events were assessed as possibly or probably related to treatment.
  
  
  
  Dalbavancin pediatric dosing that matched adult exposure was identified. Overall, dalbavancin was well tolerated in our study population.
authors.affiliation: From the*Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; †University of California San Diego School of Medicine and Rady Children's Hospital, San Diego, California; ‡University of Toledo Medical Center, Toledo, Ohio; §Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; ¶Department of Pediatrics, Duke University Medical Center, and ‖Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina; **Arkansas Children's Hospital Research Institute and University of Arkansas for Medical Sciences, Little Rock, Arkansas; ††Infectious Diseases Section, Baylor College of Medicine, Houston, Texas; ‡‡College of Pharmacy and Department of Pediatrics, University of Michigan, Ann Arbor, Michigan; §§Kosair Charities Pediatric Clinical Research Unit, Department of Pediatrics, University of Louisville, and ¶¶Kosair Children's Hospital, Louisville, Kentucky; ‖‖Institute for Clinical Pharmacodynamics, Latham, New York; and ***Durata Therapeutics, a subsidiary of Actavis plc, Branford, Connecticut.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzalez
authors.forename: John S
authors.initials: JS
authors.lastname: Bradley
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Blumer
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Watt
authors.forename: Laura P
authors.initials: LP
authors.lastname: James
authors.forename: Debra L
authors.initials: DL
authors.lastname: Palazzi
authors.forename: Varsha
authors.initials: V
authors.lastname: Bhatt-Mehta
authors.forename: Janice E
authors.initials: JE
authors.lastname: Sullivan
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Murphy
authors.forename: Xilla T
authors.initials: XT
authors.lastname: Ussery
authors.forename: Sailaja
authors.initials: S
authors.lastname: Puttagunta
authors.forename: Michael W
authors.initials: MW
authors.lastname: Dunne
authors.forename: Michael
authors.initials: M
authors.lastname: Cohen-Wolkowiez
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001424:Bacterial Infections / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D005260:Female; D006760:Hospitalization; D006801:Humans; D007223:Infant; D008297:Male; D017334:Teicoplanin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin; C469289:dalbavancin