Population pharmacokinetics and dosing optimisation of ceftazidime in infants [PublishAheadOfPrint]

Objective: Ceftazidime, a third-generation cephalosporin, can be used for thetreatment of adults and children with infections due to susceptible bacteria. To date, the pediatric pharmacokinetic data is limited in infants, and therefore we aimed to evaluate the population pharmacokinetics of ceftazidime in infants and define the appropriate dose to optimize ceftazidime treatment.

Methods: Blood samples were collected from children treated with ceftazidime, and concentrations of drug were quantified by HPLC-UV. A population pharmacokinetic analysis was performed using NONMEM software (version 7.2.0).

Results: Fifty-one infants (age range: 0.1-2.0 years) were included. Sparse pharmacokinetic samples (n = 90) were available for analysis. A one-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that body weight, and CL_CR were significant covariates influencing ceftazidime clearance. Monte Carlo simulation demonstrated that the currently used dosing regimen of 50 mg/kg twice daily was associated with a high risk of underdosing in infants. In order to reach the target 70% the time of free antimicrobial drug concentration above the minimum inhibitory concentration (fT>MIC), 25 mg/kg q8h and 50 mg/kg q8h were required for a MIC 4 mg/liter and for a MIC 8 mg/liter, respectively.

Conclusion: The population pharmacokinetics characteristics of ceftazidime were evaluated in infants. An evidence-based dosing regimen was established based on simulation.

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