눈에 묻으면 몇 분간 물로 조심해서 씻으시오. 가능하면 콘택트렌즈를 제거하시오. 계속 씻으시오.
Sivelestat sodium C화학적 특성, 용도, 생산
개요
Sivelestat is an acyl enzyme inhibitor of neutrophil elastase, developed as an injectable
formulation for the treatment of acute lung injury associated with systemic inflammatory
response syndrome. A neutrophil predominant inflammation associated with excessive
release of human neutrophil elastase (HNE) from azurophilic granules is capable of
damaging both the lung parenchymal cells and the extracellular matrix allowing an alveolar
capillary barrier disruption. Sivelestat is a sulfonanilide-containing pivaloyloxy benzene
derivative prepared in a three step synthesis. This agent acts as a reversible and selective
inhibitor of HNE with an lG.0 value of 0.044 PM. Sivelestat has exhibited potent protective
effects against various causes of lung injuries in animal models. In an acid-induced acute
lung injury model in conscious hamster, administration of sivelestat for 48 h following HCI
instillation, dose-dependently reduced mortality and significantly improved the protein
levels in bronchoalveolar lavage fluids and pulmonary artery pressure. In a similar study,
the agent inhibited the endotoxin-induced acute lung dysfunctions (marked elevation of
pulmonary vascular permeability, leukocyte migration, hemorrhage and parenchymal
injury) in different animal species. Moreover, in a cardiopulmonary bypass model in dog,
sivelestat ameliorated the respiratory index and interstitial-intra-alveolar edema. Sivelestat
has a relatively poor bioavailability, due to an extensive first-pass metabolism and is easily
hydrolyzed in vitro to an inactive metabolite. In two animal species, the half-life time was
approximately 5-7 min. Clinical trials have shown that treatment with the agent improves
respiratory function and facilitates early removal of patients from mechanical ventilation.
However, in the last clinical study, conducted by Eli Lilly in patients with acute lung injury,
no difference in mortality and safety was seen between sivelestat and placebo.
