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

OBJECTIVES

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.

METHODS

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 V 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 (CL).

RESULTS

The data was described by a two-compartment model and the values of parameter estimates for CL, V, Q and V were 5.27 L/h, 17.2 L, 9.92 L/h and 10.6 L, respectively. The CL, 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.

CONCLUSION

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 1000 mg q8h can be considered for empirical treatment of infections in elderly patients when CL is ≤ 50 mL/min. A continuous infusion of 3000 mg daily dose is preferred if CL > 50 mL/min. However, a higher daily dose of meropenem would be required for resistant strains (MIC >8 mg/L) of bacteria if CL is >100 mL/min.