Population Pharmacokinetics of Linezolid

Phase 4

Completed

• Conditions: Methicillin-Resistant Staphylococcus AureuS
• Interventions: Drug: Linezolid

• Registration Number: NCT01200654
• Lead Sponsor: University Hospital, Toulouse

Brief Summary

Linezolid is the first of a new class of antibacterial drugs, the oxazolidinones. It has a specific inhibitory activity against Gram positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).

Dosage of 600 mg discontinuous administration twice a day was about studies in safety volunteers. The intensive care units patients, with mechanical ventilation, and with severe sepsis, represent highly heterogeneous population responsible of hight variability in pharmacokinetics parameters (augmentation in total volume of distribution, modification in glomerular filtration) wich can lead to antibiotic inefficacy.

In a first time, this study describe the pharmacokinetics of Linezolid in intensive care units patients with severe MRSA infection. The aim of this study is to define and validate a population pharmacokinetic model including the influence of patients' characteristic on the pharmacokinetics of Linezolid.

Detailed Description

The demographic, clinical and biological parameters are collected. Patients receive Linezolid as 600 mg twice a day during an administration of 60 minutes.

Blood sampling are collected on the second day after beginning of treatment at the following time : H1, H2, H3, H6 and H12.

The population pharmacokinétics analysis will be carried out using Monolix, a software for the analysis of nonlinear mixed effects models.

Study Timeline

• Study Start: 2007-11
• Primary Completion: 2010-08
• Study Completion: 2010-08
• Study First Submitted: 2010-09-10
• Study First Submitted QC: 2010-09-10
• Study First Posted: 2010-09-13
• Status Verified: 2012-10
• Last Update Submitted: 2012-10-22
• Last Update Posted: 2012-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• In-patient stay in intensive care
• Over 18 years old
• Presenting with MRSA nosocomial pneumonia or bacteraemia with a strain thought to be sensitive to Linezolid
• Simplified Acute Physiological Score (SAPS) II > 20
• Expected duration of life > 7 days.

Exclusion Criteria

• History of allergy to linezolid or any of the antibiotics used
• Isolation of MRSA resistant to linezolid
• Lack of seeds
• Pregnancy and lactation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MRSA Infections	Linezolid	Methicillin-Resistant Staphylococcus aureus Infections

Primary Outcome Measures

Name	Time	Method
The first objective of this study is to research the influence of patients' characteristic on the pharmacokinetics of Linezolid.	Blood sampling are collected on the second day after begining of treatment at the following time : H1, H2, H3, H6 and H12.	The following demographic, clinical and biological parameters were collected as possible covariates: age, gender, bodyweight, height, etiology of incoming, mechanical ventilation, serum creatinine, proteins, Blood Urea Nitrogen (BUN), leukocyte counts, haemoglobin, C-reactive protein (CRP), and simplified acute physiology scores (SAPS I and II).

Secondary Outcome Measures

Name	Time	Method
The secondary outcome measure are the verification of the clinical and bactériological efficacies, and to look after the residual concentration	At the 48th hours of treatment