Population pharmacokinetics of meropenem in elderly patients: dosing simulations based on renal function.

Abstract

The aim of this study was to evaluate different dosage regimens of meropenem in elderly patients in relation with renal function using a population pharmacokinetic (popPK) model. The data of 178 elderly patients treated with meropenem was collected from different sources. A popPK model was developed by using NONMEM® and the influence of different covariates on meropenem CL and V1 was observed. Monte Carlo dosing simulations were performed at steady state to observe the % T>MIC for targets of 40, 60 and 80% of dosage intervals at different levels of creatinine clearance (CLCR). The data was described by a two-compartment model and the values of parameter estimates for CL, V1, Q and V2 were 5.27L/h, 17.2L, 9.92L/h and 10.6L, respectively. The CLCR, body weight and centre had a significant influence on meropenem CL while no direct influence of age was observed. Extended infusions had pharmacokinetic and pharmacodynamic (PK/PD) breakpoint one dilution greater than corresponding short infusion regimens for each target of % T>MIC. Meropenem CL was significantly lower in the elderly compared to CL reported in younger patients due to the reduced renal function. An extended infusion of 1000mg q8h can be considered for empirical treatment of infections in elderly patients when CLCR is ≤50mL/min. A continuous infusion of 3000mg daily dose is preferred if CLCR>50mL/min. However, a higher daily dose of meropenem would be required for resistant strains (MIC >8mg/L) of bacteria if CLCR is >100mL/min.