Population Pharmacokinetics of Linezolid

Phase 4CompletedNCT01200654

University Hospital, Toulouse60 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Methicillin-Resistant Staphylococcus AureuS

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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).

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

Secondary Outcomes

The secondary outcome measure are the verification of the clinical and bactériological efficacies, and to look after the residual concentration

Time frame: At the 48th hours of treatment