Population pharmacokinetics of meropenem in Vietnamese adult patients

Meropenem is a broad-spectrum antimicrobial frequently used for serious infections. Understanding the pharmacokinetics of meropenem is crucial in optimizing the dosage regimen to treat critically ill patients but there has been no report on its population pharmacokinetic parameters for Vietnamese adult patients. The aim of our study was to develop a population model to describe the pharmacokinetics of meropenem in Vietnamese adult patients. A prospective study was conducted in 30 patients. Plasma meropenem concentrations were measured during the first dose infusion using 6 samples per patient. Concentration-time data were analyzed using a nonlinear mixed-effects modeling approach with MONOLIXSuit2016. Eight participants' covariates were analyzed to identify their potential influence on meropenem pharmacokinetics. The adequacy of the constructed model was assessed by good-of-fit plots and the precision of the parameters estimated. Data comprised 173 meropenem concentration measurements. A 2-compartment model with zero-order input and first-order elimination showed the best fit for the data. Creatinin clearance and vasopressor use were two influential covariates for clearance: CL (L/h) = 4.74 x exp(0.019 x (CL CR -51 mL/min)) if vasopressor was used and CL (L/h) = 9.97 x exp(0.019 x (CL CR -51 mL/min)) if vasopressor was not used. The intercompartmental clearance (Q), volume of the central compartment (V c ), volume of the peripheral compartment (V p ) were estimated as 36.5 L/h, 9.24 L, 11.7 L, respectively. The inter-individual variability of CL, Q, V c , V p were 35.2%, 54.8%, 59.4% and 35.0%, respectively. The additive error was 0.0197 mg/L and the proportional error was 30.9%. � Faculty of Pharmacy, Mahidol University (Thailand) 2018.