Determination of Single-dose Intrapulmonary Pharmacokinetics of Ciprofloxacin and Imipenem in Healthy Subjects and Intubated Patients Suffering From Pneumonia Using Bronchoalveolar Lavage
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Cmax (peak concentration in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (microdose)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects aged 18 to 55 years
- •Good state of health (mentally and physically)
- •Body mass index within a range of 18 to 28kg/m2 inclusive.
- •Non-Smoker
- •A signed and dated written informed consent form.
- •The subject is able to understand and willing to comply with protocol requirements and timetables, instructions and protocol-stated restrictions.
- •Negative serology (human immunodeficiency virus, hepatitis B-AG and C-AB) at screening.
- •Vital signs should be within the following ranges:
- •Oral or tympanic temperature between 35 and 37.5°C.
- •Systolic blood pressure, 90-140 mmHg.
- •Diastolic blood pressure, 50-90 mmHg.
- •Pulse rate, 50-90 bpm.
排除标准
- •Any acute or chronic illness or clinically relevant (Investigator's judgement) abnormality identified on the screening medical assessment, laboratory tests or ECG, unless in the opinion of the Investigator it will not interfere with the study procedures, affect the outcome of the study or compromise the safety of the subject.
- •All subjects with known seizure disorder, with the exception of a febrile seizure in childhood
- •Use of prescription or non-prescription drugs within 7 days or 10 times the elimination half-life (whichever is longer) prior to the first dose of study medication.
- •Any intake of grapefruit juice within 1 week prior to the first dose.
- •Allergies (except for mild forms of hay fever), a history of hypersensitivity reactions including psychological or neurological symptoms or signs, or anaphylactic shock following administration of any medicine.
- •Allergy to or any contraindication against the active or inactive ingredients in the study medication (ciprofloxacin, imipenem, cilastatin, propofol, midazolam, remifentanil, xylocain, and sevoflurane) and radioactive labelling with 14C.
- •Alcohol or drug abuse
- •Participation in a trial with any drug within 30 days or five half-lives (whichever is longer) before the start of the study.
- •Donation of blood within a period of 4 weeks prior to dosing.
- •Creatinine clearance ≤70mL/min/1.73m3
- •Any other reason that the Investigator considers to make the subject unsuitable to participate.
研究组 & 干预措施
Ciprofloxacin
Half of patients and healthy volunteers are receiving ciprofloxacin, the other half imipenem.
干预措施: Ciprofloxacin (Drug)
Imipenem
Half of patients and healthy volunteers are receiving ciprofloxacin, the other half imipenem.
干预措施: Imipenem (Drug)
结局指标
主要结局
Cmax (peak concentration in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (microdose)
时间窗: Plasma sampling over 10 hours and microdialysate sampling.
Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.
Cmax (peak concentration in plasma and epithelial lining fluid) of imipenem and ciprofloxacin
时间窗: Plasma over 10 hours and BAL (bronchoalveolar lavage) Sampling at different time points in these 10 hours.
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.
AUC (area under the concentration curve in plasma and epithelial lining fluid) of imipenem and ciprofloxacin.
时间窗: Plasma over 10 hours and BAL Sampling at different time points in these 10 hours.
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.
Tmax (time of peak concentration in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (microdose)
时间窗: Plasma sampling over 10 hours and microdialysate sampling.
Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.
Tmax (time of peak concentration in plasma and epithelial lining fluid) of imipenem and ciprofloxacin.
时间窗: Plasma over 10 hours and BAL Sampling at different time points in these 10 hours.
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.
AUC (area under the curve in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (carbon-14 radiolabelled compound, microdose)
时间窗: Plasma sampling over 10 hours and microdialysate sampling.
Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.
Cmax (peak concentration in microdialysate) of ciprofloxacin (macrodose)
时间窗: Microdialysate sampling (Baseline sampling before study drug administration - sampling over 3 hours - retrodialysis)
In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.
AUC (area under the concentration curve in microdialysate) of ciprofloxacin (macrodose)
时间窗: Microdialysate sampling (Baseline sampling before study drug administration - sampling over 3 hours - retrodialysis)
In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.
Tmax (time of peak concentration in microdialysate) of ciprofloxacin (macrodose)
时间窗: Microdialysate sampling (Baseline sampling before study drug administration - sampling over 3 hours - retrodialysis)
In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.
次要结局
- Incidence of Treatment Emergent Adverse Events(Screening visit and final examination are performed up to 7 days before/after the actual study day and safety and tolerability assessed.)
研究者
Markus Zeitlinger
Professor Dr.
Medical University of Vienna