Clinical trial NCT01983839: PK Analysis of Moxifloxacin in the Treatment of CAP
Official title: Moxifloxacin Pharmacokinetic Profile and Efficacy Evaluation in the Empiric Treatment of Community-Acquired Pneumonia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pneumonia
Keywords: Moxifloxacin
Pneumonia
Pharmacokinetics
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2013-11-14
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with community-acquired pneumonia, treated with moxifloxacin, admitted to the Department of Infectious diseases, Aarhus University Hospital, Denmark

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.

Eligibility criteria: Inclusion Criteria:

* Patients with community-acquired pneumonia, treated with moxifloxacin

Exclusion Criteria:

* Under 18 years of age

Primary outcomes:
measure: Total Peak Plasma Concentration (Cmax)
timeFrame: The second day of Moxifloxacin treatment
measure: Area Under the Free Concentration-time Curve (fAUC0-24)
timeFrame: The second day of Moxifloxacin treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Infectious Diseases, Aarhus University Hospital
state: Aarhus N
Study officials:
affiliation: Department of Infectious Diseases, Aarhus University Hospital, Denmark
name: Eskild Petersen, MD, Assoc. Prof., D.Sc.
role: STUDY_DIRECTOR
References:
citation: Obrink-Hansen K, Hardlei TF, Brock B, Jensen-Fangel S, Kragh Thomsen M, Petersen E, Kreilgaard M. Moxifloxacin pharmacokinetic profile and efficacy evaluation in empiric treatment of community-acquired pneumonia. Antimicrob Agents Chemother. 2015 Apr;59(4):2398-404. doi: 10.1128/AAC.04659-14. Epub 2015 Feb 9.