Sivelestat sodium tetrahydrate is a competitive inhibitor of human neutrophil elastase (HNE) (IC50 = 44 nM, Ki = 0.2 M). Sivelestat sodium tetrahydrate also effectively inhibits leukocyte elastase derived from hamster, mouse, rabbit and rat (IC50 = 19 to 49 nM). Sivelestat sodium tetrahydrate, even at concentrations of 100 M, does not inhibit plasma kallikrein, plasmin, thrombin, trypsin, pancreas kallikrein, chymotrypsin and cathepsin G. In in-vivo studies, sivelestat sodium tetrahydrate suppressed lung hemorrhage in hamster (ID50 = 82 g/kg) by intratracheal administration and increased skin capillary permeability in guinea pigs (ID50 = 9.6 mg/kg) by intravenous administration, both of which were induced by human neutrophil elastase.
