Population pharmacokinetics of meropenem in critically ill children with different renal functions

We aimed to develop a meropenem population pharmacokinetic (PK) model in critically ill children and simulate dosing regimens in order to optimize patient exposure.

Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem PK was investigated using a non-linear mixed-effect modeling approach.

Forty patients with an age of 16.8 (1.4-187.2) months, weight of 9.1 (3.8-59) kg, and estimated glomerular filtration rate (eGFR) of 151 (19-440) mL/min/1.73 m² were included. Eleven patients received continuous replacement renal therapy (CRRT). Concentration-time courses were best described by a two-compartment model with first-order elimination. Body weight (BW), eGFR, and CRRT were covariates explaining the between-subject variabilities on central/peripheral volume of distribution (V1/V2), inter-compartment clearance (Q), and clearance (CL): V1_i = V1_pop × (BW/70)¹, Q_i = Q_pop × (BW/70)^0.75, V2_i = V2_pop × (BW/70)¹, CL_i = (CL_pop × (BW/70)^0.75) × (eGFR/100)^0.378) for patients without CRRT and CL_i = (CL_pop × (BW/70)^0.75) × 0.9 for patients with CRRT, where CL_pop, V1_pop, Q_pop, and V2_pop are 6.82 L/h, 40.6 L, 1 L/h, and 9.2 L respectively normalized to a 70-kg subject. Continuous infusion, 60 and 120 mg/kg per day, is the most adequate dosing regimen to attain the target of 50% fT > _MIC and 100% fT > _MIC for patients infected by bacteria with high minimum inhibitory concentration (MIC) value (> 4 mg/L) without risk of accumulation except in children with severe renal failure.

Continuous infusion allows reaching the fT > _MIC targets safely in children with normal or increased renal clearance.