Population pharmacokinetics/pharmacodynamics of linezolid in sepsis patients with and without continuous renal replacement therapy.

Abstract

PURPOSE:

The purpose of this study was to identify the optimum dosing regimen of linezolid in sepsis patients with and without renal dysfunction and sepsis patients on low-dose continuous renal replacement therapy (CRRT) using a pharmacokinetics/pharmacokinetics (PK/PD) approach.

METHODS:

Sepsis patients with and without renal dysfunction (creatinine clearance < 50 mL/min), and sepsis patients on low-dose CRRT (dose: 800 mL/h) were studied. The PK data were modeled using a two-compartment model, and then used for simulation. The target PK/PD was the 24-h area under the concentration-time curve to minimum inhibitory concentration ratio of ≥ 80. Dosing regimens were evaluated using cumulative fraction of response (CFR) and safety probability (trough level < 7 µg/mL) by Monte Carlo simulation.

RESULTS:

Twenty-seven patients, including 8 patients with preserved renal function, 9 patients with renal dysfunction, and 10 patients on CRRT, were studied. The proposed regimen to attain CFR ≥ 90% was 800 mg every 12 h (safety probability 82.4%) for patients with preserved renal function. By contrast, the target CFR was attained with a decreased regimen in patients with renal dysfunction and those on CRRT [600 mg every 24h (safety probability 68.6%) and 800 mg every 24h (42.1%)].

CONCLUSIONS:

We identified different dosage strategies to achieve target linezolid concentrations according to renal function and use of CRRT in sepsis patients. Because of unassured safety probability in patients without preserved renal function, dosing regimens should be adjusted based on the therapeutic drug monitoring.

• Authors: Takeshi Ide, Yoshio Takesue, Kazuro Ikawa, Norifumi Morikawa, Takashi Ueda, Yoshiko Takahashi, Kazuhiko Nakajima, Kenta Takeda, Shinichi Nishi
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 51 Issue 5 Pg. 745-751 (May 2018) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 29425834 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Linezolid

Topics

• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (administration & dosage, blood, pharmacokinetics)
• Area Under Curve
• Humans
• Kidney (physiopathology)
• Linezolid (administration & dosage, blood, pharmacokinetics)
• Middle Aged
• Monte Carlo Method
• Prospective Studies
• Renal Replacement Therapy (methods)
• Sepsis (drug therapy)
• Staphylococcal Infections (drug therapy)