Sivelestat (ONO-5046, 0.021-2.1 mg/kg, intratracheally) suppresses lung hemorrhage in hamster (ID 50 = 82 pg/kg) by intratracheal administration and increase of skin capillary permeability in guinea pig (ID 50 = 9.6 mg/kg) by intravenous administration, both of which are induced by human neutrophil elastase. Sivelestat (10 mg/kg, infusion via the tail vein) ameliorates lung injury after hemorrhagic shock in rats. Sivelestat (15, 60 mg/kg, ip) prevents ischemia–reperfusion injury in the rat bladder. Animal Model: Male Golden hamsters, weighing 90 to 110 g. Dosage: 0.021-2.1 mg/kg. Administration: Intratracheally five min before HNE injection. Result: Significantly and dosedependently suppressed the lung hemorrhage. Animal Model: Male Sprague-Dawley rats weighing 350-400 g. Dosage: 10 mg/kg. Administration: Continuous infusion via the tail vein at 10 mg/kg/h for 60 min during the resuscitation phase. Result: Greatly suppressed lung injury, as revealed by the reduced histological damage. Significantly ameliorated HSR-induced lung injury. Markedly decreased the levels of TNF-α and iNOS gene. Animal Model: Male Sprague Dawley rats, 8 weeks old and weighing 250-320 g. Dosage: 15 mg/kg or 60 mg/kg. Administration: IP. Result: Decreased the blood flow in the bladder during reperfusion phase compared to the IR group.

Sivelestat (ONO-5046) does not inhibit trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin and cathepsin G even at 100 μM. Sivelestat (ONO-5046) exhibits IC 50 values of 44 nM, 36 nM, 19 nM, 37 nM and 49 nM for human, rabbit, rat, hamster and mouse neutrophil elastase, respectively.

Sivelestat (EI546) sodium 是竞争性的人类中性粒细胞弹性蛋白酶的抑制剂，其IC50 值为 44 nM， Ki 值为 200 nM。Sivelestat (EI546) sodium 有潜力用于COVID-19 的急性肺损伤/急性呼吸窘迫综合征或弥散性血管内凝血的研究。