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Population Pharmacokinetics and Pharmacodynamics of Meropenem in Pediatric Patients
Author(s) -
Du Xiaoli,
Li Chonghua,
Kuti Joseph L.,
Nightingale Charles H.,
Nicolau David P.
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005283283
Subject(s) - meropenem , pharmacokinetics , medicine , nonmem , pharmacodynamics , population , volume of distribution , antibiotics , pharmacology , carbapenem , population pharmacokinetics , biology , microbiology and biotechnology , antibiotic resistance , environmental health
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.