The investigators will determine the difference of pharmacokinetics of ciprofloxacin and imipenem between healthy volunteers and intensive care patients suffering from pneumonia in plasma and at the target site - lung - using bronchoalveolar lavage. As additional aspect the feasibility of combining microdosing of C14 ciprofloxacin with microdialysis, saliva sampling and bronchoalveolar lavage is studied by comparing pharmacokinetics of microdose and macrodose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
10
Ciprofloxacin 400mg will be administered as single dose infusion over 60 minutes, imipenem/cilastatin 1000mg as single intravenous dose applicated over 60 minutes.
Ciprofloxacin 400mg will be administered as single dose infusion over 60 minutes, imipenem/cilastatin 1000mg as single intravenous dose applicated over 60 minutes.
Medical University of Vienna
Vienna, Austria
Cmax (peak concentration in plasma and epithelial lining fluid) of imipenem and ciprofloxacin
Comparison of Cmax of ciprofloxacin and imipenem in plasma and epithelial lining fluid, alveolar macrophages and saliva (only healthy subjects) in healthy subjects and patients with bacterial pneumonia.
Time frame: Plasma over 10 hours and BAL (bronchoalveolar lavage) Sampling at different time points in these 10 hours.
AUC (area under the concentration curve in plasma and epithelial lining fluid) of imipenem and ciprofloxacin.
Comparison of AUC of ciprofloxacin and imipenem in plasma and epithelial lining fluid, alveolar macrophages and saliva (only healthy subjects) in healthy subjects and patients with bacterial pneumonia.
Time frame: Plasma over 10 hours and BAL Sampling at different time points in these 10 hours.
Tmax (time of peak concentration in plasma and epithelial lining fluid) of imipenem and ciprofloxacin.
Comparison of AUC of ciprofloxacin and imipenem in plasma and epithelial lining fluid, alveolar macrophages and saliva (only healthy subjects) in healthy subjects and patients with bacterial pneumonia.
Time frame: Plasma over 10 hours and BAL Sampling at different time points in these 10 hours.
Cmax (peak concentration in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (microdose)
Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.
Time frame: Plasma sampling over 10 hours and microdialysate sampling.
AUC (area under the curve in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (carbon-14 radiolabelled compound, microdose)
Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.
Time frame: Plasma sampling over 10 hours and microdialysate sampling.
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Tmax (time of peak concentration in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (microdose)
Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.
Time frame: Plasma sampling over 10 hours and microdialysate sampling.
Cmax (peak concentration in microdialysate) of ciprofloxacin (macrodose)
In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.
Time frame: Microdialysate sampling (Baseline sampling before study drug administration - sampling over 3 hours - retrodialysis)
AUC (area under the concentration curve in microdialysate) of ciprofloxacin (macrodose)
In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.
Time frame: Microdialysate sampling (Baseline sampling before study drug administration - sampling over 3 hours - retrodialysis)
Tmax (time of peak concentration in microdialysate) of ciprofloxacin (macrodose)
In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.
Time frame: Microdialysate sampling (Baseline sampling before study drug administration - sampling over 3 hours - retrodialysis)
Incidence of Treatment Emergent Adverse Events
Incidence of Treatment Emergent Adverse Events (Study drugs: ciprofloxacin, 14C labelled ciprofloxacin and imipenem)
Time frame: Screening visit and final examination are performed up to 7 days before/after the actual study day and safety and tolerability assessed.