Population pharmacokinetics and pharmacodynamics of meropenem in pediatric patients.
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.
Du
Xiaoli
X
Center for Anti-infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA.
Li
Chonghua
C
Kuti
Joseph L
JL
Nightingale
Charles H
CH
Nicolau
David P
DP
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003401:Creatine / Q000652:urine; D004334:Drug Administration Schedule; D019741:Haemophilus influenzae type b / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007668:Kidney / Q000378:metabolism; D008581:Meningitis / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D015337:Multicenter Studies as Topic; D009345:Neisseria meningitidis / Q000187:drug effects / Q000302:isolation & purification; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000302:isolation & purification; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem; D003401:Creatine