Clinical trial NCT01200654: Population Pharmacokinetics of Linezolid
Official title: Population Pharmacokinetics of Linezolid in Intensive Care Units Patients Treated for Methicillin-Resistant Staphylococcus Aureus (MRSA) Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Methicillin-Resistant Staphylococcus AureuS
Keywords: Population pharmacokinetics
Linezolid
Monolix
nonlinear mixed effects models
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2010-09-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The first objective of this study is to research the influence of patients' characteristic on the pharmacokinetics of Linezolid.
timeFrame: Blood sampling are collected on the second day after begining of treatment at the following time : H1, H2, H3, H6 and H12.
Secondary outcomes:
measure: The secondary outcome measure are the verification of the clinical and bactériological efficacies, and to look after the residual concentration
timeFrame: At the 48th hours of treatment
Other outcomes:
Locations:
Study officials:
affiliation: UH Toulouse
name: Bernard Georges, PhMD
role: PRINCIPAL_INVESTIGATOR
References: