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

Purpose We aimed to develop a meropenem population pharmacokinetic (PK) model in critically ill children and simulate dosing regimens in order to optimize patient exposure. Methods Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem PK was investigated using a non-linear mixed-effect modeling approach. Results 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 m(2) 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) x (BW/70)(1), Q(i) = Q(pop) x (BW/70)(0.75), V2(i) = V2(pop) x (BW/70)(1), CLi = (CLpop x (BW/70)(0.75)) x (eGFR/100)(0.378)) for patients without CRRT and CLi = (CLpop x (BW/70)(0.75)) x 0.9 for patients with CRRT, where CLpop, 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. Conclusion Continuous infusion allows reaching the fT > (MIC) targets safely in children with normal or increased renal clearance.