Pharmacokinetic of Ceftriaxone in Septic ICU Patients

Study Overview
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Brief Summary
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Ceftriaxone pharmacokinetics variability in intensive care unit septic patients In intensive care units, drug dosage is often based on study made on healthy volunteers or on less severe patients. However, pharmacokinetic alterations have been described for some drugs used in intensive care units. These alterations, consequences of alteration of volume of distribution, of protein concentrations, of impaired hepatic and renal functions can result in accumulation with toxicity or  under dosage  with inefficacity. Ceftriaxone is an antibiotic often prescribed in intensive care unit. However, despite this large utilisation, very few data is available on the pharmacokinetic in intensive care unit, and optimal dosage is not known. Our objective is to develop a population pharmacokinetics model of ceftriaxone in intensive care unit patients with sepsis, severe sepsis and septic shock and to identify the  data  explaining interindividual variability of each pharmacokinetics parameter.

Detailed Description
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This is a one centre population pharmacokinetics non interventional study. One group of 50 patients allows the development of the model and a second group of 20 patients will be used for the validation of the model. Septic patients treated with ceftriaxone according to standard procedure of our ICU could be included before the second administration of the drug. In the development group, patients will underwent five determination of serum concentration of ceftriaxone during the 24 hours following the second administration. The timing of samples will be randomised in three groups. A second phase of sampling will take place during the fifth day of ceftriaxone therapy for sepsis and severe sepsis patients and after 48 hours catecholamine- free for septic shock patients. For the validation group, ten samples will be obtained at the same periods. This study will not induce any change in the care of patients. Samples will be centrifugated immediately after collection and conserved at - 20 °C. Ceftriaxone will be assayed in the department of pharmacology, university of Marseille France, usig HPLC method. Pharmacokinetic analysis will used NONlinear Mixed Effects Modelling logiciel

Official Title
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Pharmacokinetics Variability of Ceftriaxone in Septic ICU Patients

Conditions
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Sepsis, Severe Sepsis, Septic Shock

Intervention / Treatment
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* Drug: ceftriaxone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighteen-year or more sepsis, severe sepsis or septic shock (according to Bone's criteria) admission to intensive care unit informed consent obtained affiliation to medicare Exclusion Criteria: Previous haemodialysis hemopathy known allergy to cephalosporin patients whose death is considered imminent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ceftriaxone|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum drug concentration |  |  | 
| pharmacokinetics parameter (plasmatic half-life, clearance, ...) |  |  | 
| ratio of serum drug concentration on MCI |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Ceftriaxone, Pharmacokinetic, Intensive care unit