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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.

journal_name

Ther Drug Monit

journal_title

Therapeutic drug monitoring

authors

Niibe Y,Suzuki T,Yamazaki S,Suzuki T,Takahashi N,Hattori N,Nakada TA,Oda S,Ishii I

doi

10.1097/FTD.0000000000000741

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

588-594

issue

eissn

0163-4356

issn

1536-3694

pii

00007691-202008000-00011

journal_volume

pub_type

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