The pharmacokinetics of meropenem in infants and children: a population analysis.
Plasma meropenem concentration versus time data collected during a single dose, pharmacokinetic study in infants and children were analysed using the population pharmacokinetics program NONMEM. A total of 300 meropenem concentrations was obtained from 65 patients ranging from 2 months to 12 years of age; weighing between 3.7 and 46 kg. A two-compartment open pharmacokinetic model with a zero-order infusion over 30 min was fitted to the data. The most important determinant of meropenem clearance was the creatinine clearance but an additional improvement occurred when a nonlinear dependence upon age was included. The most important determinant of the volume of distribution in the central and peripheral compartments was the body weight. The distributional clearance showed a nonlinear dependence on body weight. Demographic factors other than weight and age were not found to be influential in the model. Both clearance and distributional clearance were markedly different in the younger (< 2 years) or lighter (< 10 kg) patients, respectively. Thereafter the parameter values slowly approached those found in adults. In this study, a mean of 4.6 samples per patient was used to provide information on the pharmacokinetics and the determinants of the pharmacokinetic variability in infants and children. The findings in the younger, lighter patients, if generally applicable, might have significance for the dosage recommendations for drugs with narrow therapeutic indices.
Zeneca Pharmaceuticals, Mereside, Macclesfield, Cheshire, UK.
E M
EM
Parker
M
M
Hutchison
J L
JL
Blumer
D000367:Age Factors; D000704:Analysis of Variance; D001424:Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D001835:Body Weight; D015780:Carbapenems / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000032:analysis; D006801:Humans; D007223:Infant; D000077731:Meropenem; D008954:Models, Biological; D013845:Thienamycins / Q000493:pharmacokinetics*
D015780:Carbapenems; D013845:Thienamycins; D003404:Creatinine; D000077731:Meropenem