1970. Dalbavancin Pharmacokinetics and Safety in Children 3 Months to 11 Years of Age
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Dalbavancin_IDWeek_Poster_20161019.pdf (329.6 kB)
  • 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, multi-center 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 using NONMEM (ver. 7.1.2). We then used the model to perform simulations and identified pediatric dosing that matches exposure observed in the phase 3 adult studies.

    Results: The dataset used for PK model development included 311 dalbavancin plasma concentrations from 43 subjects. The median (range) age and dose were 5.9 years (0.3-16.9) and 400 mg (60–1000). A three-compartment, linear PK model described the data well. Based on simulations, the following age-dependent dosing regimens were found to achieve similar exposure to that in adults receiving a 2-dose regimen (1000 mg on day 1 and 500 mg given on day 8): age 6 to < 18 years, 12 mg/kg (1000 mg maximum) on day 1 and 6 mg/kg (500 mg maximum) on day 8; age 3 months to < 6 years, 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 regimens were found to match adult exposure after a single-dose (1500 mg): age 6 to < 18 years, 18 mg/kg (1500 mg maximum) on day 1, and age 3 months to < 6 years, 22.5 mg/kg (1500 mg maximum) on day 1. Thirty-six treatment-emergent adverse events were reported; 5 of which were possibly or probably related to dalbavancin.

    Conclusion: Dalbavancin pediatric dosing that matches adult exposure was identified. Overall, dalbavancin was well tolerated in our study population.

    Daniel Gonzalez, PharmD, PhD1, John S. Bradley, MD, FIDSA, FPIDS2, Jeffrey Blumer, MD, PhD3, Ram Yogev, MD4, Kevin Watt, MD5, Laura James, MD6, Debra Palazzi, MD7, Varsha Bhatt-Mehta, PharmD, MS8, Janice Sullivan, MD9, Li Zhang, M.D., Ph.D.10, Jennifer Murphy, PhD5, Xilla Ussery, MD11, Sailaja Puttagunta, MD11, Michael Dunne, MD12 and Michael Cohen-Wolkowiez, MD, PhD5, (1)Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, (2)Pediatric Infectious Diseases, Rady Children’s Hospital, University of California at San Diego School of Medicine, San Diego, CA, (3)Department of Pediatrics, University of Toledo, Toledo, OH, (4)Department of Pediatrics, Ann & Robert Lurie Children’s Hospital of Chicago, Chicago, IL, (5)Duke Clinical Research Institute, Durham, NC, (6)Arkansas Children Research Institute, Little Rock, AR, (7)Baylor College of Medicine, Houston, TX, (8)University of Michigan, Ann Arbor, MI, (9)University of Louisville, Louisville, KY, (10)Institute for Clinical Pharmacodynamics, Schenectady, NY, (11)Durata Therapeutics, Inc., Branford, CT, (12)Iterum Therapeutics (formerly of Allergan, plc), Old Saybrook, CT

    Disclosures:

    D. Gonzalez, None

    J. S. Bradley, Durata Therapeutics, Inc.: Investigator , Research support

    J. Blumer, Durata Therapeutics, Inc.: Investigator , Research support

    R. Yogev, Durata Therapeutics, Inc.: Investigator , Research support

    K. Watt, Durata Therapeutics, Inc.: Investigator , Research support

    L. James, Durata Therapeutics, Inc.: Investigator , Research support

    D. Palazzi, Durata Therapeutics, Inc.: Investigator , Research support

    V. Bhatt-Mehta, Durata Therapeutics, Inc.: Investigator , Research support

    J. Sullivan, Durata Therapeutics, Inc.: Investigator , Research support

    L. Zhang, Durata Therapeutics, Inc.: Research Contractor , Financial support

    J. Murphy, Durata Therapeutics, Inc.: Employee at the Duke Clinical Research Institute, which has a contract with Durata Therapeutics, Inc. to perform this study. , Research support

    X. Ussery, Allergan, Inc.: Consultant , Consulting fee

    S. Puttagunta, Allergan, Inc.: Employee , Salary and Stock options

    M. Dunne, Allergan, Inc.: Employee , Salary and Speaker honorarium

    M. Cohen-Wolkowiez, Durata Therapeutics, Inc.: Investigator , Research support

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.