Population Pharmacokinetic Analysis of Meropenem in Critically Ill Patients With Acute Kidney Injury Treated With Continuous Hemodiafiltration.

Abstract

BACKGROUND:

The aim of this study was to conduct a population pharmacokinetic (PK) analysis of meropenem and to explore the optimal dosing strategy for meropenem in critically ill patients with acute kidney injury receiving treatment with continuous hemodiafiltration (CHDF).

METHODS:

Blood samples were obtained on days 1, 2, and 5 after the start of meropenem administration, immediately before dosing, and at 1, 2, 6, and 8 hours after dosing. Population PK model analysis was performed and concentration-time profiles were simulated using the Nonlinear Mixed Effects Model software.

RESULTS:

Twenty-one patients receiving CHDF in our intensive care unit were enrolled and 350 serum concentration-time data points were obtained. The PKs of meropenem were best described using a 2-compartment model. Typical total and intercompartmental clearance values were 4.22 L/h and 7.84 L/h, respectively, whereas the central and peripheral compartment volumes of distribution were 14.82 L and 11.75 L, respectively. Estimated glomerular filtration rate was identified as a significant covariate of meropenem total clearance. In simulations of patients with renal failure receiving CHDF, the dose was affected by estimated glomerular filtration rate; a dose of 0.5 g every 8 hours or 1 g every 12 hours showed the probability of target attainment of achieving 100% time above the minimum inhibitory concentration for bacteria with a minimum inhibitory concentration ≤2 mg/L.

CONCLUSIONS:

A population PK model was developed for meropenem in critically ill patients with acute kidney injury receiving CHDF. Our results indicated that a meropenem dosage of 0.5 g every 8 hours or 1 g every 12 hours was suitable in this population and for susceptible bacteria.

• Authors: Yoko Niibe, Tatsuya Suzuki, Shingo Yamazaki, Takaaki Suzuki, Nozomi Takahashi, Noriyuki Hattori, Taka-Aki Nakada, Shigeto Oda, Itsuko Ishii
• Journal: Therapeutic drug monitoring (Ther Drug Monit) Vol. 42 Issue 4 Pg. 588-594 (08 2020) ISSN: 1536-3694 [Electronic] United States
• PMID: 32049890 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Meropenem

Topics

• Acute Kidney Injury (metabolism)
• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (pharmacokinetics)
• Critical Illness
• Female
• Hemodiafiltration (methods)
• Humans
• Infusions, Intravenous (methods)
• Intensive Care Units
• Male
• Meropenem (pharmacokinetics)
• Metabolic Clearance Rate (physiology)
• Microbial Sensitivity Tests (methods)
• Middle Aged
• Prospective Studies
• Renal Dialysis (methods)
• Young Adult