Population Pharmacokinetics of Prolonged Infusion for Meropenem: Tailoring Dosing Recommendations for Chinese Critically Ill Patients on Continuous Renal Replacement Therapy with Consideration for Renal Function.

Abstract

Objective: Extended meropenem infusion is increasingly employed to enhance clinical outcomes in critically ill patients. Nonetheless, investigations into such dosing regimens in renal-impaired patients undergoing continuous renal replacement therapy (CRRT) are scarce. This study aims to perform a population pharmacokinetic (PK) analysis of prolonged meropenem infusion in critically ill CRRT patients to inform optimal dosing regimens.

Methods: Ninety-four concentrations from 21 Chinese critically ill CRRT patients receiving 1 g meropenem every 8-12 hours infused over 2-3 hours were utilized to construct the population PK model. Monte Carlo simulations were employed to assess the efficacy based on PK/PD targets (100% fT_>MIC or 100% fT_>4×MIC) and the risk of nephrotoxicity (trough concentration ≥45 mg/L) for extended meropenem dosing regimens (0.5-2 g with a 3-hour infusion administered every 6-12 hours).

Results: Meropenem concentration data was adequately described by a one-compartment model with linear elimination, and creatinine clearance (CLCR) significantly influenced meropenem's endogenous clearance. 0.5 g q6h and 1 g q8h could achieve desirable attainment of 100% fT_>MIC target against an MIC≤4 mg/L, with negligible risk of toxicity for CRRT patients across a CLCR range of 10-50 mL/min. 2 g q6h and 2 g q8h is required for targeting 100% fT_>4×MIC for the patients, but the associated risk of toxicity is very high (>20%).

Conclusion: A population PK model was developed for prolonged meropenem infusion in Chinese CRRT patients, and 0.5 g q6h and 1 g q8h may be the optimal regimen for prolonged infusion.