THE PHARMACOKINETICS OF MEROPENEM IN INFANTS AND CHILDREN - A POPULATION ANALYSIS

Plasma meropenem concentration versus time data collected during a sin gle dose, pharmacokinetic study in infants and children were analysed using the population pharmacokinetics program NONMEM. A total of 300 m eropenem concentrations was obtained from 65 patients ranging from 2 m onths to 12 years of age; weighing between 3.7 and 46 kg. A two-compar tment open pharmacokinetic model with a zero-order infusion over 30 mi n was fitted to the data. The most important determinant of meropenem clearance was the creatinine clearance but an additional improvement o ccurred when a nonlinear dependence upon age was included. The most im portant determinant of the volume of distribution in the central and p eripheral compartments was the body weight. The distributional clearan ce showed a nonlinear dependence on body weight. Demographic factors o ther 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 adu lts. In this study, a mean of 4.6 samples per patient was used to prov ide information on the pharmacokinetics and the determinants of the ph armacokinetic variability in infants and children. The findings in the younger, lighter patients, if generally applicable, might have signif icance for the dosage recommendations for drugs with narrow therapeuti c indices.