39 Population pharmacokinetics of meropenem in neonatal and pediatric extracorporeal membrane oxygenation: a retrospective pilot study (preliminary analysis)

Introduction Meropenem is a broad-spectrum antibiotic commonly used to treat serious infections in the pediatric population treated with extracorporeal membrane oxygenation (ECMO). It is known that ECMO may affect the drug's pharmacokinetics (PK) by altering the drug's clearance (CL), volume of distribution (Vd), and protein binding. There are limited data on ECMO influence on PK of meropenem in neonates and children undergoing ECMO. Therefore, the aim of this study was to describe PK of meropenem in critically ill neonates and children undergoing ECMO. Methodology Data from therapeutic drug monitoring (TDM) were available from 25 (14 female, 11 male) critically ill patients (median (interquartile range, IQR), body weight (BW): 5 (3.28–13.50) kg; postnatal age (PNA): 124 (15–1008) days) treated with meropenem (average intermittent dose of 20 mg/kg or continuous infusion), of whom 15 received veno-venous (VV) or veno-arterial (VA) ECMO. Meropenem levels ranged between 0.68 and 67 mg/L. Population PK analysis was performed using NONMEM V7.3.0. The following covariates were tested: maturation variables: BW, PNA; disease status: laboratory values, including serum creatinine, serum urea, serum albumin, total bilirubin, blood pH, aspartate transaminase, and alanine transaminase; concomitant therapy: use of diuretics, inotropes, as well as use of continuous renal replacement therapy; ECMO variables: on/off ECMO, duration of ECMO treatment, ECMO flow rate. Results According to the model, PNA is a covariate for both CL and Vd, while BW is a covariate of CL. ECMO and CRRT have no significant impacts on the PK parameters. In a one-compartment model, CL and Vd for a typical child of median BW (5 kg) at median PNA (124 days) are 0.459 L/h (RSE = 22.7%)) and 1.76 L (47.3%), respectively. The coefficients of variation for inter-individual variability (IIV) for CL and Vd are 51.5% (17.6%) and 26.9% (22.3%), respectively. A proportional error with a coefficient of variation of 42.7% (9.8%) provides the best description of the residual variability. Conclusion ECMO does not affect the PK of meropenem in the cohort. Further larger studies should confirm these results. Acknowledgments: Pfizer Grant 69506665, and colleagues A. Alvarsson and M.Ch. Johansson.