Developments in the pharmacokinetic/pharmacodynamic index of linezolid: a step toward dose optimization using Monte Carlo simulation in critically ill patients.

Abstract

OBJECTIVES:

This study evaluated the efficacy of the pharmacokinetic/pharmacodynamic (PK/PD) index for increasing the success rate of linezolid treatment based on Monte Carlo simulation, and compared differences between the calculated PK/PD breakpoints and those defined by committee for critically ill patients with linezolid treatment.

METHODS:

A Monte Carlo simulation involving 10000 subjects was used to analyze the pharmacokinetic parameters and microbiological data of linezolid for an effectiveness evaluation at the corresponding AUC24/MIC values (area under the serum concentration-time curve over 24h/minimum inhibitory concentration).

RESULTS:

As the PK/PD index of linezolid increased from 80 to 120, the corresponding probability of target attainment (PTA) decreased from 99.91% to 18.97%, with a MIC of 2mg/l. Furthermore, the cumulative fraction of response (CFR) reached <90% for several pathogens at an AUC24/MIC of 100-120, revealing a relatively lower efficacy with recommended linezolid dosing.

CONCLUSIONS:

These findings reveal that the target AUC24/MIC value of 80-120 requires further classification for more accurate assessment of the linezolid dose regimen. At a MIC of ≥2mg/l, the clinical outcome varies greatly for different AUC24/MIC values when applying the same dose of linezolid. In such cases, we suggest optimized adjustment of the linezolid dosage regimen.

• Authors: Haiyan Dong, Jiao Xie, Lihong Chen, Taotao Wang, Jinyue Sun, Yingren Zhao, Yalin Dong
• Journal: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (Int J Infect Dis) Vol. 22 Pg. 35-40 (May 2014) ISSN: 1878-3511 [Electronic] Canada
• PMID: 24603161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Acetamides
• Anti-Bacterial Agents
• Oxazolidinones
• Linezolid

Topics

• Acetamides (blood, pharmacokinetics, pharmacology)
• Anti-Bacterial Agents (blood, pharmacokinetics, pharmacology)
• Area Under Curve
• Computer Simulation
• Critical Illness
• Drug Dosage Calculations
• Drug Resistance, Multiple, Bacterial
• Enterococcus (drug effects, physiology)
• Gram-Positive Bacterial Infections (blood, drug therapy, microbiology)
• Humans
• Linezolid
• Methicillin-Resistant Staphylococcus aureus (drug effects, physiology)
• Microbial Sensitivity Tests
• Models, Statistical
• Monte Carlo Method
• Oxazolidinones (blood, pharmacokinetics, pharmacology)
• Streptococcus pneumoniae (drug effects, physiology)