Pneumonia
Conditions
Keywords
Moxifloxacin, Pneumonia, Pharmacokinetics
Brief summary
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
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.
Interventions
None listed
Sponsors
University of Aarhus
Study design
Observational model
CASE_ONLY
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with community-acquired pneumonia, treated with moxifloxacin
Exclusion criteria
* Under 18 years of age
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Peak Plasma Concentration (Cmax) | The second day of Moxifloxacin treatment | 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) |
| Area Under the Free Concentration-time Curve (fAUC0-24) | The second day of Moxifloxacin treatment | 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) |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pharmacokinetics Moxifloxacin Patients with diagnosed CAP who were prescribed moxifloxacin 400 mg qd (Avelox® 400 mg Bayer) empirically by the treating physician, according to national CAP treatment guideline, had plasma concentrations of moxifloxacin determined. Patients under 18 years of age were excluded from the study and the age, gender and body weight of each enrolled patient were registered. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Pharmacokinetics Moxifloxacin |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 73 years |
| Body weight | 72.6 kg |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
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)
Time frame: The second day of Moxifloxacin treatment
Population: The model estimated median values of fAUC0-24 for the current study population were32.78 mg.hr/L (IQR 22.75; 47.31). respectively.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pharmacokinetics Moxifloxacin | Area Under the Free Concentration-time Curve (fAUC0-24) | 32.78 mg.hr/L |
Primary
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)
Time frame: The second day of Moxifloxacin treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pharmacokinetics Moxifloxacin | Total Peak Plasma Concentration (Cmax) | 3.99 mg/L |