Cystic fibrosis, a common lethal genetic disorder, is characterized by a neutrophilic inflammatory exudate in the airways which causes bronchiectasis and eventual respiratory failure. Neutrophil elastase is believed to mediate many of the pathologic processes such as destruction of airway supporting tissue, mucus hypersecretion, opsonic deficiency, and cytokine secretion. DMP777 is a synthetic monobactam that penetrates the neutrophil to inhibit both intra- and extracellular elastase in a selective and essentially irreversible fashion. This study is a dose-escalating protocol to examine safety, pharmacokinetics, and pharmacodynamics of DMP777 in patients with CF by direct measurement of drug levels and elastase inhibition in bronchoalvolar fluids.
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