Population Pharmacokinetics of Linezolid

Population Pharmacokinetics of Linezolid in Intensive Care Units Patients Treated for Methicillin-Resistant Staphylococcus Aureus (MRSA) Infections

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.

Study Overview

• Status: Completed
• Conditions: Methicillin-Resistant Staphylococcus AureuS
• Intervention / Treatment: Drug: 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 Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MRSA Infections; Methicillin-Resistant Staphylococcus aureus Infections	Drug: Linezolid; Dosage of 600 mg discontinuous administration twice a day was about studies in safety volunteers; Other Names: Pharmacokinetics of Linezolid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The first objective of this study is to research the influence of patients' characteristic on the pharmacokinetics of Linezolid.	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).	Blood sampling are collected on the second day after begining of treatment at the following time : H1, H2, H3, H6 and H12.

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Bernard Georges, PhMD, UH Toulouse

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: September 10, 2010
• First Submitted That Met QC Criteria: September 10, 2010
• First Posted (Estimate): September 13, 2010

Study Record Updates

• Last Update Posted (Estimate): October 23, 2012
• Last Update Submitted That Met QC Criteria: October 22, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Linezolid; Population pharmacokinetics; Monolix; nonlinear mixed effects models
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Staphylococcal Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Linezolid
• Other Study ID Numbers: 06 049 02