Use of Ceftazidime-Avibactam in Infants and Children

Marcia L. Buck, PharmD, FCCP, FPPAG, BCPPS

Disclosures

Pediatr Pharm. 2019;25(5) 

In This Article

Pharmacokinetics

Ceftazidime-avibactam exhibits linear pharmacokinetics.[2] Less than 10% of the administered dose is bound to serum proteins. It is excreted by the kidneys, with 80–90% of the dose eliminated as unchanged drug. Approximately 50% of the dose is excreted within 2 hours of dose administration. Elimination is decreased in patients with renal impairment, requiring dosage adjustment to avoid drug accumulation and toxicity.

The pharmacokinetic profile of ceftazidime-avibactam was evaluated as part of a phase 1 safety and tolerability study conducted in 32 children.[8] Patients were divided into four cohorts: 1 (12 years to up to 18 years of age), 2 (6 years up to 12 years), 3 (2 years up to 6 years), and 4 (3 months up to 2 years). A single dose was given over 2 hours: 2 grams for cohort 1 and 50 mg/kg up to a maximum of 500 mg in cohorts 2–4. Mean maximum plasma ceftazidime concentrations (Cmax) for the four cohorts were 79.8 mg/L (CV% 41.8), 81.3 mg/L (17.8), 80.1 mg/L (14.7), and 91.7 mg/L (19.6), respectively. Additional parameters were only evaluated in the two older cohorts. Area under the concentration-time curve (AUC) results were also similar to adult values, with a mean of 230.6 hr•mg/L (30.7) in cohort 1 and 221.2 hr•mg/L (17.4) in cohort 2. Mean elimination half-lives for the two cohorts were 1.7 hours (range 0.9–2.8 hours) and 1.6 hours (0.9–1.8 hours). Likewise, avibactam Cmax was similar across all four cohorts: 15.1 mg/L (52.4), 14.1 mg/L (23.1), 13.7 mg/L (22.4), and 16.3 mg/L (22.6). Values for avibactam AUC in cohorts 1 and 2 were 36.4 hr•mg/L (33.6) and 34.8 hr•mg/L (22.6), and half-lives for groups 1 and 2 were 2.0 hours (2.9–2.6 hours) and 2.1 hours (1.9–2.4), respectively.

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