Pharmacokinetics and pharmacodynamics of meropenem in children with severe infection

Abstract

This study aimed to describe the pharmacokinetic (PK) characteristics of meropenem in children with severe infections and to assess the pharmacokinetic/pharmacodynamic (PK/PD) profiles of various meropenem dosage regimens in these patients. Fourteen children with severe infections received intravenous (i.v.) bolus doses of meropenem (20 mg/kg/dose) every 8 h (q8h). Serum samples were obtained before and serially after the second dose of meropenem, and a population PK analysis was performed. The final model was used to simulate serum concentration–time profiles with various dosage regimens. The PK/PD target was to achieve a serum meropenem concentration higher than the minimum inhibitory concentration (MIC) of the causative organism (i.e. Pseudomonas aeruginosa and Enterobacteriaceae) for ≥40% of the dosing interval (40%T>MIC). The median age and weight of the children were 6.0 years and 20.0 kg, respectively. Meropenem serum concentration–time profiles were best described by a two-compartmental model with first-order elimination. The simulations showed that the probabilities of target attainment (PTAs) for organisms with an MIC of 1 mg/L were 0.678 and 1.000 following i.v. bolus and 3-h infusion of meropenem (20 mg/kg/dose), respectively. Using a 3-h infusion of a 20 mg/kg/dose, the PTA was 0.999 and 0.765 for organisms with MICs of 4 mg/L and 8 mg/L, respectively. Meropenem given as i.v. bolus doses of 20 mg/kg/dose q8h appeared to be inadequate for PK/PD target attainment for organisms with an MIC of 1 mg/L. The simulations showed that meropenem administration via a 3-h infusion using the same dose improved the PTA.