PK Analysis of Moxifloxacin in the Treatment of CAP

Study Overview
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Brief Summary
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At the Department of Infectious Diseases, Aarhus Denmark, moxifloxacin is used in the empirical treatment of severe community-acquired pneumonia (CAP). This study was designed to determine the pharmacokinetics of moxifloxacin 400 mg/day to patients treated empirically for CAP. To accomplish this aim, we established a pharmacokinetic population model. This approach was adopted with the dual purpose of assessing the potential efficacy of the drug and performing Monte-Carlo simulations to characterize the maximal MICs for which recommended pharmacokinetic-pharmacodynamic (PK-PD) targets are obtained for pathogens commonly known to cause CAP.

Detailed Description
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We determined the pharmacokinetic profile of moxifloxacin 400 mg/day in 18 patients treated empirically for community-acquired pneumonia. . Moxifloxacin plasma concentrations were determined the day after therapy initiation using ultra high performance liquid chromatography. The moxifloxacin plasma concentration-time profiles were described with a one compartment model, using NONMEM. Peak drug concentrations (Cmax) and 24-hour area under the free drug concentration-time curve values (fAUC0-24) predicted for each patient were evaluated against epidemiological cut-off MIC values for Streptococcus pneumoniae, Haemophilus influenzae and Legionella pneumophilia. PK-PD targets adopted were Cmax/MIC ≥ 12.2 for all pathogens, fAUC0-24/MIC > 34 for S. pneumoniae and fAUC0-24/MIC > 75 for H. influenzae and L. pneumophilia. The same PK-PD estimates were used in the simulations of probability of target attainment (PTA) versus MIC.

Official Title
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Moxifloxacin Pharmacokinetic Profile and Efficacy Evaluation in the Empiric Treatment of Community-Acquired Pneumonia

Conditions
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Pneumonia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with community-acquired pneumonia, treated with moxifloxacin Exclusion Criteria: Under 18 years of age

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pharmacokinetics Moxifloxacin<br>Patients with community-acquired pneumonia treated with moxifloxacin | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Peak Plasma Concentration (Cmax) | The moxifloxacin plasma concentration-time profiles were described with a one compartment model with first-order absorption and elimination rate. The model estimated median values of total Cmax for the current study population were reported. Each individual model predicted Cmax were divided by the ECOFF MIC for S. pneumoniae (0.5 mg/L), H. influenzae (0.125 mg/L) and L. pneumophilia (1.0 mg/L) | The second day of Moxifloxacin treatment | 
| Area Under the Free Concentration-time Curve (fAUC0-24) | The moxifloxacin plasma concentration-time profiles were described with a one compartment model with first-order absorption and elimination rate. The model estimated median values of fAUC0-24 for the current study population were reported. fAUC0-24 were divided by the ECOFF MIC for S. pneumoniae (0.5 mg/L), H. influenzae (0.125 mg/L) and L. pneumophilia (1.0 mg/L) | The second day of Moxifloxacin treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moxifloxacin, Pneumonia, Pharmacokinetics