Population pharmacokinetics and pharmacodynamics of meropenem in pediatric patients

J Clin Pharmacol. 2006 Jan;46(1):69-75. doi: 10.1177/0091270005283283.

Abstract

Meropenem is a highly potent carbapenem antibiotic against gram-positive and gram-negative bacteria. Meropenem plasma concentration data from 99 pediatric patients (aged 0.08-17.3 years) were used to develop a population pharmacokinetic model. Pharmacokinetic analysis was performed using NONMEM with exponential interindividual variability and combinational residual error model. A 2-compartment model was found to fit the data best. Creatinine clearance and body weight were the most significant covariates explaining variabilities in meropenem pharmacokinetics among pediatric patients. The validated final model was used to predict meropenem plasma concentrations in 37 pediatric meningitis patients, receiving 40 mg/kg meropenem, who had minimum inhibitory concentration values of the causative pathogens and outcome available. Since the causative pathogens in all patients were eradicated, no break points for required exposure could be found. The microbiological outcomes indicate that the current clinical dosage regimen provides sufficient drug exposure to eradicate the pathogens commonly involved in pediatric meningitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Body Weight
  • Child
  • Child, Preschool
  • Clinical Trials as Topic
  • Creatine / urine
  • Drug Administration Schedule
  • Haemophilus influenzae type b / drug effects
  • Haemophilus influenzae type b / isolation & purification
  • Humans
  • Infant
  • Kidney / metabolism
  • Meningitis / drug therapy
  • Meningitis / metabolism*
  • Meningitis / microbiology
  • Meropenem
  • Microbial Sensitivity Tests
  • Models, Biological
  • Multicenter Studies as Topic
  • Neisseria meningitidis / drug effects
  • Neisseria meningitidis / isolation & purification
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / isolation & purification
  • Thienamycins / administration & dosage
  • Thienamycins / pharmacokinetics*
  • Thienamycins / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Thienamycins
  • Meropenem
  • Creatine