[Pharmacological profile of a specific neutrophil elastase inhibitor, Sivelestat sodium hydrate].
Imbalance between neutrophil elastase (NE) and its endogenous protease inhibitors has been considered to be one of possible mechanisms by which NE causes lung tissue destruction. It has been shown that the amount and/or activity of NE is increased in blood and bronchoalveolar lavage fluid in patients with acute lung injury. Accordingly, animals undergoing acute lung injury have increased NE activity such as in blood and bronchoalveolar lavage fluid. Sivelestat sodium hydrate (Sivelestat) is a synthetic inhibitor of NE with highly specificity to NE. Many studies have indicated that Sivelestat treatment improves inflammatory and edematous changes of lungs and survival as well as increased NE activity in several animal models of acute lung injury. Clinical studies have demonstrated that Sivelestat improves this injury that is associated with systemic inflammatory response syndrome. As compared with endogenous protease inhibitors that have high molecular mass, Sivelestat, a synthetic and low molecular weight elastase inhibitor, may be delivered to the inflammatory sites more easily and effectively and is considred to improve typical symptoms of acute lung injury. Clinical use of Sivelestat would further clarify the usefulness of this compound in clinical acute lung injury.
Kawabata
Kazuhito
K
Discovery Research Laboratory II, Minase Research Institute, Ono Pharmaceutical Co., Ltd., Mishima, Osaka, Japan.
Hagio
Tetsuya
T
Matsuoka
Shozo
S
D000818:Animals; D017326:Clinical Trials, Phase III as Topic; D004195:Disease Models, Animal; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000502:physiology / Q000633:toxicity; D015843:Serpins / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy / Q000201:enzymology
D015843:Serpins; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine