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Antimicrob Agents Chemother. 2016 Sep 23;60(10):6252-9. doi: 10.1128/AAC.00862-16. Print 2016 Oct.

Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients.

Author information

1
University of California, San Diego, California, USA jbradley@rchsd.org.
2
AstraZeneca, Macclesfield, United Kingdom.
3
Children's Hospital of Orange County, Orange, California, USA.
4
AstraZeneca, Gaithersburg, Maryland, USA.
5
Children's Hospital & Medical Center, Omaha, Nebraska, USA.
6
AstraZeneca, Wilmington, Delaware, USA.
7
AstraZeneca, Waltham, Massachusetts, USA.
8
West Virginia University, Morgantown, West Virginia, USA.
9
University of Toledo, Toledo, Ohio, USA.
10
University of Texas Health Science Center, Houston, Texas, USA.
11
University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Arkansas, USA.
12
University Hospitals Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA.
13
University of Louisville and Kosair Children's Hospital, Louisville, Kentucky, USA.

Abstract

This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0-∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.).

PMID:
27503642
PMCID:
PMC5038276
DOI:
10.1128/AAC.00862-16
[Indexed for MEDLINE]
Free PMC Article

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