Phase i study assessing the pharmacokinetic profile, safety, and tolerability of a single dose of ceftazidime-avibactam in hospitalized pediatric patients

John S. Bradley, Jon Armstrong, Antonio Arrieta, Raafat Bishai, Shampa Das, Shirley Delair, Timi Edeki, William C. Holmes, Jianguo Li, Kathryn S. Moffett, Deepa Mukundan, Norma Perez, José R. Romero, David Speicher, Janice E. Sullivan, Diansong Zhou

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6252-6259
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number10
DOIs
StatePublished - Oct 2016
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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