Pulmonary pharmacokinetics and safety of nebulized duramycin in healthy male volunteers
Naunyn-Schmiedeberg's archives of pharmacology(2008)
摘要
Duramycin (Moli1901) is being developed for the treatment of reduced mucociliary clearance in cystic fibrosis. This study was conducted to estimate lung residence time and systemic exposure and to assess whether duramycin causes an inflammatory response. Six volunteers were administered a single dose (7.5 mg) of nebulized duramycin and underwent bronchoscopies to obtain a composite data set for pharmacokinetic analysis; duramycin was measured in the cellular fraction of bronchoalveolar lavage fluid (BALF) (mainly alveolar macrophages) and brush biopsies (bronchial epithelial cells). The estimated t 1/2 of duramycin was ∼5 days in brush biopsies and 25 to 91 days in BALF cells. Levels of duramycin in BALF ( C max 800 ng/mg) exceeded those in brush biopsies by ∼20-fold. Duramycin was absent from plasma and did not cause any detectable inflammatory response in pulmonary tissue as judged from the BALF profile of 14 relevant cytokines. Our data suggest that duramycin qualifies for intrapulmonary administration in cystic fibrosis (CF) patients.
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关键词
Moli1901,Duramycin,Cystic fibrosis,Pulmonary pharmacokinetics,Broncheoalveloar lavage,Brush biopsy
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