Population pharmacokinetics and dose optimization of ceftriaxone for children with community-acquired pneumonia

Eur J Clin Pharmacol. 2020 Nov;76(11):1547-1556. doi: 10.1007/s00228-020-02939-4. Epub 2020 Jun 25.

Abstract

Purpose: To assess ceftriaxone population pharmacokinetics in a large pediatric population and describe the proper dose for establishing an optimized antibiotic regimen.

Methods: From pediatric patients using ceftriaxone, blood samples were obtained and the concentration was measured using high-performance liquid chromatography ultraviolet detection. The NONMEM software program was used for population pharmacokinetic analysis, for which data from 99 pediatric patients (2 to 12 years old) was collected and 175 blood concentrations were obtained.

Results: The best fit with the data was shown by the one-compartment model with first-order elimination. According to covariate analysis, weight had a significant impact on the clearance of ceftriaxone. Using Monte Carlo simulation, in a pediatric population with community-acquired pneumonia, a dose regimen of 100 mg/kg every 24 h produced satisfactory target attainment rates while remaining within the required minimum inhibitory concentration (2 mg/L).

Conclusion: Population pharmacokinetics of ceftriaxone was evaluated in children and an optimum dosing regimen was constructed on the basis of the pharmacokinetics-pharmacodynamics model-based approach.

Keywords: Ceftriaxone; Children; Community-acquired pneumonia; Dosing regimen.

MeSH terms

  • Ceftriaxone / administration & dosage
  • Ceftriaxone / pharmacokinetics*
  • Child
  • Child, Preschool
  • Community-Acquired Infections / drug therapy*
  • Humans
  • Models, Biological
  • Monte Carlo Method
  • Pneumonia / drug therapy*

Substances

  • Ceftriaxone