Population Pharmacokinetics of Linezolid

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT01200654
First received: September 10, 2010
Last updated: October 22, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Methicillin-Resistant Staphylococcus AureuS
Drug: Linezolid
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Population Pharmacokinetics of Linezolid in Intensive Care Units Patients Treated for Methicillin-Resistant Staphylococcus Aureus (MRSA) Infections

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • The first objective of this study is to research the influence of patients' characteristic on the pharmacokinetics of Linezolid. [ Time Frame: Blood sampling are collected on the second day after begining of treatment at the following time : H1, H2, H3, H6 and H12. ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: November 2007
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01200654

Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Principal Investigator: Bernard Georges, PhMD UH Toulouse
  More Information

No publications provided

Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT01200654     History of Changes
Other Study ID Numbers: 06 049 02
Study First Received: September 10, 2010
Last Updated: October 22, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Toulouse:
Population pharmacokinetics
Linezolid
Monolix
nonlinear mixed effects models

Additional relevant MeSH terms:
Staphylococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Linezolid
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014