Development of an Adjustment Assistance Tool Dosage of Fluoroquinolones in a Population Pharmacokinetic Model

Study Overview
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Brief Summary
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Fluoroquinolones (FQ) are among pivotal antibiotic treatments in difficult-to-treat infections. Their efficacy has been shown to be linked to the ratio area under the curve (AUC) of their plasma concentrations over the minimum inhibitory concentration (MIC) of the bacteria treated. Eventually, Forrest et al., reported in gram-negative infections that an AUC/MIC above 125 conducted to a 80 to 90% clinical success whereas success decrease to 30 to 40% in patients with an AUC/MIC below this threshold. These results have been reproduced recently by Zelenitsky et al. in intensive care unit (ICU) patients with threshold similar to the one obtained by Forrest et al. Lastly, elevated concentrations of FQ should be related with the onset of adverse events. Thus, therapeutic drug monitoring (TDM) of FQ appears of potential interest, particularly in case of severe infections (intensive care unit (ICU) patients) or complicated and cost-related infections (osteoarticular infected (OAI) patients), with an increasing level of evidence of its use. However, FQ TDM requires access to the full AUC of the drug with the need of many samples drawn to patients. This appears to be irreconcilable with clinical practice but can be achieved using population pharmacokinetic (PkPop) modelling. PkPop allows estimating pharmacokinetic parameters of the drug by introducing covariates (demographic, biological, clinical…) and modelling inter-individual pharmacokinetic variability. The model created allows then accessing to individual parameters of patients and thus, estimating concentrations and AUC of the FQ. This approach may also be used in clinical practice to determine a limited sampling strategy allowing an adequate estimation of AUC with a minimum of samples.

Detailed Description
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Open, prospective, monocentric pharmacokinetic study

Official Title
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Development of an Adjustment Assistance Tool Dosage of Fluoroquinolones in a Population Pharmacokinetic Model

Conditions
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Infection

Intervention / Treatment
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* Drug: Patients in intensive care : infection treated with ciprofloxacin IV
* Drug: Osteoarticular infected patients : infection treated with oral ofloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 18 years Patients in intensive care : Infection treated with ciprofloxacin IV Osteoarticular infected patients : infection treated with oral ofloxacin Written consent to participate in the study Exclusion Criteria: Pregnancy Adults subject to legal protection or deprived of their liberty

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients in intensive care<br>30 patients in intensive care treated with ciprofloxacin IV | Drug: Patients in intensive care : infection treated with ciprofloxacin IV<br>* 8-10 samples per patients on day-4 of their treatment<br>* Other names: Blood samples;|
| Experimental: Osteoarticular infected patients<br>30 patients in orthopedics treated with oral ofloxacin | Drug: Osteoarticular infected patients : infection treated with oral ofloxacin<br>* 8-10 samples per patients on day-4 of their treatment<br>* Other names: Blood samples;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration measurement of ciprofloxacin and ofloxacin | measurement between 2 administrations (8-10 samples per patients) | on day-4 of their treatment (steady-state) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demographic data |  | on day-4 of their treatment (steady-state) | 
| Biological data |  | on day-4 of their treatment (steady-state) | 
| Clinical data |  | on day-4 of their treatment (steady-state) | 
| AUC |  | on day-4 of their treatment (steady-state) | 
| MIC |  | on day-4 of their treatment (steady-state) | 
| Cmax |  | on day-4 of their treatment (steady-state) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fluoroquinolones, pharmacokinetic, infections