Meropenem Pharmacokinetics and Target Attainment in Critically Ill Patients.

Abstract

This study aimed to investigate the pharmacokinetics and target attainment of meropenem and compare the effect of meropenem dosing regimens in critically ill patients. Thirty-seven critically ill patients who were administered meropenem in intensive care units were analyzed. Patients were classified according to their renal function. Pharmacokinetic parameters were assessed based on Bayesian estimation. The target attainment of 40%fT > MIC (fraction time that the free concentration exceeds the minimum inhibitory concentration) and 100%fT > MIC with the pathogen MIC of 2 mg/L and 8 mg/L were specially focused. Furthermore, the effects of standard dosing (1g meropenem, 30 min intravenous infusion every 8h) and non-standard dosing (dosage regimens except standard dosing) were compared. The results showed that the values of meropenem clearance (CL), central volume of distribution (V1), intercompartmental clearance (Q), and peripheral volume of distribution (V2) were 3.3 L/h, 9.2 L, 20.1 L/h and 12.8 L, respectively. The CL of the patients among renal function groups was significantly different (p < 0.001). The tow targets attainment for the pathogen MIC of 2 mg/L and 8 mg/L were 89%, 73%, 49% and 27%, respectively. The severe renal impairment group has higher fraction of target attainment than the other group. The standard dosing achieved the target of 40%fT > 2/8 mg/L (85.7% and 81%, respectively) and patients with severe renal impairment achieved the target fraction of 100% for 40%fT > MIC. Additionally, there was no significant difference between standard and non-standard dosing group in target attainment. Our findings indicate that renal function is an important covariate for both meropenem pharmacokinetics parameters and target attainment. The target attainment between standard and non-standard dosing group was not comparable. Therefore, therapeutic drug monitoring is indispensable in the dosing adjustment for critically ill patients if it is available.