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Population Pharmacokinetics and Dosing Optimization of Imipenem in Children with Hematological Malignancies

Lei Dong1, Xiao-Ying Zhai2, Yi-Lei Yang3

  • 1Department of Pharmacy, Children's Hospital of Hebei Province, Shijiazhuang, China.

Antimicrobial Agents and Chemotherapy
|April 10, 2019
PubMed

Insights

This study found that current imipenem dosages may underdose children with hematological malignancies against resistant bacteria. However, the 25 mg/kg every 6 hours dose is acceptable for sensitive pathogens in this population.

Area of Science:

  • Pharmacology
  • Pediatric Oncology
  • Infectious Diseases

Background:

  • Imipenem is crucial for treating serious pediatric infections.
  • Pharmacokinetic data for imipenem in children with hematological malignancies are limited.
  • Disease and drug resistance necessitate optimized dosing strategies.

Purpose of the Study:

  • To conduct a population pharmacokinetic analysis of imipenem in children with hematological malignancies.
  • To optimize imipenem dosage regimens for improved therapeutic outcomes in this vulnerable group.

Main Methods:

  • Population pharmacokinetic analysis using NONMEM software.
  • Quantification of imipenem concentrations via high-performance liquid chromatography with UV detection.
  • Analysis of data from 56 children (aged 2.03–11.82 years) with hematological malignancies.

Main Results:

  • A two-compartment model with first-order elimination best described imipenem pharmacokinetics.
  • Weight, age, and creatinine elimination rate were significant covariates.
  • Dosages of 15, 20, and 25 mg/kg q6h achieved pharmacodynamic targets against sensitive pathogens (MIC 0.5 mg/L) in 41.4%, 56.1%, and 67.1% of children, respectively.
  • Only 11.1% achieved the target against Pseudomonas aeruginosa (MIC 2 mg/L) at 25 mg/kg q6h.

Conclusions:

  • Current imipenem dosing may lead to underdosing against resistant pathogens like Pseudomonas aeruginosa and Acinetobacter baumannii.
  • A dosage of 25 mg/kg every 6 hours provides an acceptable pharmacodynamic target rate for sensitive pathogens in pediatric hematology patients.

Keywords:
childrendosingimipenempopulation pharmacokinetics

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