Oral administration of sepimostat mesilate prevents acute alcohol pancreatic injury in rats

The preventive effect of a novel synthetic serine protease inhibitor, sepim ostat mesilate (sepimostat), on acute alcohol pancreatic injury, induced by exocrine hyperstimulation and ethanol administration, was assessed and com pared with that of a similar protease inhibitor, camostat mesilate (camosta t). Conscious rats were infused with 1 mu g mL(-1) h(-1) caerulein intravenousl y for 6 h and with 0.1 g mL(-1) h(-1) ethanol for 9 h, with the latter infu sion beginning 3 h after the start of the caerulein infusion. Sepimostat or camostat was administered orally Ih before the caerulein infusion. Rats infused with caerulein plus ethanol showed increased plasma amylase an d lipase activities, and aggravated pancreatic interstitial oedema when com pared with rats given caerulein alone. Sepimostat at 10 and 30 mg kg(-1) pr evented the increase in plasma amylase and lipase activities caused by caer ulein plus ethanol infusion. Sepimostat at 30 mg kg-l suppressed the histol ogical change. Camostat did not show any preventive effects at the equivale nt dose. When conscious rats were infused with 1 mu g mL(-1) h(-1) caerulei n alone intravenously for 6 h, plasma amylase and lipase activities were in creased compared with rats given saline. Neither drug prevented the increas e in these activities at 30 mg kg(-1) Our results suggest that sepimostat has superior preventive effects on alco hol-induced acute pancreatic injury compared with camostat. Sepimostat may thus be a useful drug in the therapy of alcohol-induced pancreatitis.