Effect of FUT-175 (Nafamstat Mesilate) on Platelets in Canine Acute Experimental Pancreatitis

Abstract

In 1981, a new low-molecular-weight protease inhibitor, FUT-175 (nafamstat mesilate), was synthesized. Its preventive action against acute experimental pancreatitis (AEP) was detected. We studied the effect of FUT-175 on the blood count and aggregability of platelets in AEP in dogs. At 30 min after induction of AEP, the sensitivity to ADP increased more than two times in untreated animals. An evident decrease in platelet count of about 37% was noted in these dogs at 6h after AEP induction. Treatment of AEP with FUT-175 prevented these changes. We assume that the positive effect of FUT-175 against AEP depends at least in part on its influence on platelet aggregation.

Continuous Regional Arterial Infusion of Protease Inhibitors Has No Efficacy in the Treatment of Severe Acute Pancreatitis

“…7 In a meta-analysis, however, intravenous administration of protease inhibitors was not associated with favorable clinical outcomes such as reduced mortality rate or the need for surgical intervention, which suggests that an adequate concentration of the drug cannot be achieved, and effects on tissue arterial microcirculation are suboptimal with the intravenous formulation used. 8,9 For this reason, continuous regional arterial infusion (CRAI) of protease inhibitors, with direct delivery of a protease inhibitor into the pancreatic circulation, was proposed to potentially reduce the mortality rate and prevent the development of pancreatic infection in patients with ANP rather than SAP.…”

Mechanisms of synthetic serine protease inhibitor (FUT‐175)‐mediated cell death

“…FUT‐175, a well‐established synthetic serine protease inhibitor, has been shown to be an effective therapeutic agent for disseminated intravascular coagulation, systemic inflammatory response syndrome, and pancreatitis 11–13. FUT‐175 is a potent inhibitor of neutrophils, the complement system, the coagulation system, and the activity of many proteases such as trypsin and plasmin 14.…”