Identification of factors affecting meropenem pharmacokinetics in critically ill patients: Impact of inflammation on clearance.

INTRODUCTION

The purpose of this study was to explore factors influencing meropenem pharmacokinetics (PKs) in critically ill patients by developing a population PK model and to determine the optimal dosing strategy.

METHODS

This prospective observational study involved 12 critically ill patients admitted to the intensive care unit and treated with meropenem 1 g infused over 1 h every 8 h. Blood samples were collected on days 1, 2, and 5 immediately prior to dosing, and at 1, 2, 4, and 6 h after the start of infusion. Population PK parameters were estimated using nonlinear mixed-effects model software.

RESULTS

Meropenem PK was adequately described using a two-compartment model. Typical values of total and inter-compartmental clearance were 9.30 L/h and 9.70 L/h, respectively, and the central and peripheral compartment volumes of distribution were 12.61 L and 7.80 L, respectively. C-reactive protein (CRP) was identified as significant covariate affecting total meropenem clearance. The probability of target attainment (PTA) predicted by Monte Carlo simulations varied according to the patients' CRP. The PTA of 100% time above the minimum inhibitory concentration ≤2 mg/L for bacteria was achieved after a dose of 1 and 2 g infused over 4 h every 8 h in patients with CRP of 30 and 5 mg/dL, respectively.

CONCLUSION

The findings of this study suggest that CRP might be helpful in managing meropenem dosing in critically ill patients. Higher doses and extended infusion may be required to achieve optimal pharmacodynamic targets.