THE JOURNAL OF ANTIBIOTICS FR901451, A NOVEL INHIBITOR OF HUMAN LEUKOCYTE ELASTASE FROMFlexibacter sp. II. PHARMACOLOGICAL EFFECT OF FR901451

Intratracheal (i.t.) or intravenous (i.v.) administration of FR90145 1, a potent inhibitor of human leukocyte elastase (HLE) prevented HLE-induced lung hemorrhage in hamsters with ED50 values of 10.5 /ig/site and 8. 1 mg/kg, respectively. al-Antitrypsin (al-AT) also showed inhibitory effect in this model. However, the ED50 value by i.t. injection of FR901451was 20-fold lower than that of al-AT. Moreover, FR901451 i.t. significantly modulated porcine pancreas elastase (PPE)-induced changes of the respiratory mechanics in hamsters. The ED50 values were 529 /zg/site and 244 //g/site, which were expressed by static lung compliance (Cst) and vital capacity (VC) of the lungs, respectively. These results suggest that FR90145 1 could be clinically useful agent for the treatment of the destructive lung disease such as pulmonary emphysema. 1365