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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gonzalez, D; Bradley, JS; Blumer, J; Yogev, R; Watt, KM; James, LP; Palazzi, DL; Bhatt-Mehta, V; Sullivan, JE; Zhang, L; Murphy, J; Ussery, XT; Puttagunta, S; Dunne, MW; Cohen-Wolkowiez, M

Published Date

  • July 2017

Published In

Volume / Issue

  • 36 / 7

Start / End Page

  • 645 - 653

PubMed ID

  • 28060045

Pubmed Central ID

  • 28060045

Electronic International Standard Serial Number (EISSN)

  • 1532-0987

International Standard Serial Number (ISSN)

  • 0891-3668

Digital Object Identifier (DOI)

  • 10.1097/INF.0000000000001538

Language

  • eng