Dalbavancin Pharmacokinetics and Safety in Children 3 Months to 11 Years of Age
| Autor: | Ram Yogev, Janice E. Sullivan, Sailaja Puttagunta, Varsha Bhatt-Mehta, Kevin M. Watt, John S. Bradley, Debra L. Palazzi, Michael Cohen-Wolkowiez, Xilla T. Ussery, Li Zhang, Laura P. James, Jeffrey L. Blumer, Daniel Gonzalez, Michael W. Dunne, Jennifer Murphy |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Microbiology (medical) Gerontology Lipoglycopeptide medicine.drug_class Antibiotics Pharmacology 030226 pharmacology & pharmacy Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Area under curve medicine Humans Computer Simulation 030212 general & internal medicine Child Extramural business.industry Dalbavancin Infant Bacterial Infections Anti-Bacterial Agents Hospitalization Clinical trial Infectious Diseases Oncology chemistry Multicenter study Area Under Curve Child Preschool Pediatrics Perinatology and Child Health Female Teicoplanin business |
| Zdroj: | Open Forum Infectious Diseases. 3 |
| ISSN: | 2328-8957 |
| Popis: | 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 to18 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 to6 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 to18 years of age, 18 mg/kg (1500 mg maximum) on day 1 and 3 months to6 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. |
| Databáze: | OpenAIRE |
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