title: Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients.
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.).
authors: University of California, San Diego, California, USA jbradley@rchsd.org.
authors: John S
authors: JS
authors: Bradley
authors: AstraZeneca, Macclesfield, United Kingdom.
authors: Jon
authors: J
authors: Armstrong
authors: Children's Hospital of Orange County, Orange, California, USA.
authors: Antonio
authors: A
authors: Arrieta
authors: AstraZeneca, Gaithersburg, Maryland, USA.
authors: Raafat
authors: R
authors: Bishai
authors: AstraZeneca, Macclesfield, United Kingdom.
authors: Shampa
authors: S
authors: Das
authors: Children's Hospital & Medical Center, Omaha, Nebraska, USA.
authors: Shirley
authors: S
authors: Delair
authors: AstraZeneca, Wilmington, Delaware, USA.
authors: Timi
authors: T
authors: Edeki
authors: AstraZeneca, Gaithersburg, Maryland, USA.
authors: William C
authors: WC
authors: Holmes
authors: AstraZeneca, Waltham, Massachusetts, USA.
authors: Jianguo
authors: J
authors: Li
authors: West Virginia University, Morgantown, West Virginia, USA.
authors: Kathryn S
authors: KS
authors: Moffett
authors: University of Toledo, Toledo, Ohio, USA.
authors: Deepa
authors: D
authors: Mukundan
authors: University of Texas Health Science Center, Houston, Texas, USA.
authors: Norma
authors: N
authors: Perez
authors: University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Arkansas, USA.
authors: José R
authors: JR
authors: Romero
authors: University Hospitals Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA.
authors: David
authors: D
authors: Speicher
authors: University of Louisville and Kosair Children's Hospital, Louisville, Kentucky, USA.
authors: Janice E
authors: JE
authors: Sullivan
authors: AstraZeneca, Waltham, Massachusetts, USA.
authors: Diansong
authors: D
authors: Zhou
mesh_terms: D000293:Adolescent; D053961:Azabicyclo Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D002442:Ceftazidime / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D005260:Female; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D008297:Male; D065093:beta-Lactamase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D053961:Azabicyclo Compounds; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D065093:beta-Lactamase Inhibitors; D002442:Ceftazidime