Dalbavancin Pharmacokinetics and Safety in Children 3 Months to 11 Years of Age

Daniel Gonzalez, John S. Bradley, Jeffrey Blumer, Ram Yogev, Kevin M. Watt, Laura P. James, Debra L. Palazzi, Varsha Bhatt-Mehta, Janice E. Sullivan, Li Zhang, Jennifer Murphy, Xilla T. Ussery, Sailaja Puttagunta, Michael W. Dunne, Michael Cohen-Wolkowiez*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background: Dalbavancin is a novel lipoglycopeptide antibiotic that has potent in vitro activity against Gram-positive microorganisms. Methods: 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. Results: 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. Conclusions: Dalbavancin pediatric dosing that matched adult exposure was identified. Overall, dalbavancin was well tolerated in our study population.

Original languageEnglish (US)
Pages (from-to)645-653
Number of pages9
JournalPediatric Infectious Disease Journal
Volume36
Issue number7
DOIs
StatePublished - Jul 1 2017

Keywords

  • adolescents
  • children
  • dalbavancin
  • infants
  • pediatrics
  • pharmacokinetics
  • safety

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

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