Aprotinin in severe acute pancreatitis

Abstract

Aprotinin, a Kunitz protease inhibitor, has a wide inhibitory action with particular activity against trypsin, chymotrypsin and kallikrein, making it theoretically attractive in ameliorating the effects of acute pancreatitis. Its use in acute pancreatitis has been studied for the last 50 years with disappointing results. In this paper, we review the previous studies and argue that all the studies have not been adequately powered, have inappropriate end-points, but most importantly have not attained adequate plasma and peritoneal levels of aprotinin to produce sufficient inhibitory activity. We hypothesise that a well-powered study with adequate aprotinin dosing may clarify its clinical benefit in severe acute pancreatitis.

Effect of microemulsion formulation on biodistribution of 99mTc-Aprotinin in acute pancreatitis models induced rats

“…Aprotinin is theoretically attractive molecule in ameliorating the effects of acute pancreatitis (Bjerregaard et al, 2001;Smith et al, 2009). Over the following two decades Aprotinin therapeutic potential on pancreatitis is proven experimentally but its clinical therapeutic success is limited due to low targeting to pancreas.…”

“…Since Aprotinin is a Kunitz protease inhibitor and has action particularly against trypsin, chymotrypsin and kallikrein potent proteinase inhibitors, it is theoretically attractive molecule in ameliorating the effects of acute pancreatitis (Bjerregaard et al, 2001;Smith et al, 2009).…”

Effects of Soybean Trypsin Inhibitor on Hemostasis

“…Both blood clotting and fibrinolysis represents the cascade of proteolytic reactions catalyzed by highly specific proteases [43]. To correct disturbances of the fibrinolysis as well as imbalances of the other proteolytic processes the animal trypsin inhibitor aprotinin is used as a drug (Trasisol, Contrical, Gordox etc) [24,13,40]. The effectiveness of the aprotinin in the treatment of some diseases has been questioned recently because of it's substantial disadvantages [23,12].…”

“…Serpins participate in the regulation of proteopytic reactions underling very important physiological and pathological processes such as digestion [16], blood clotting [3,14,17], immunity [44] apoptosis [36,42], inflammation [10], dystrophy [31], carcinogenesis [22,11] and so on. Despite the apparent importance of the correction of imbalances of the proteolysis in pathology, in fact only the pancreatic trypsin inhibitor (aprotinin) is used more or less widely as a protease inhibitor drug (Trasisol, Contrical, Gordox etc) in the treatment of some diseases [24,13,40]. Being the animal protein aprotinin possesses substantial disadvantages [23,12] and attempts to develop new drug on the base of plant or recombinant proteins or peptidomimetics are undertaken [35,27].…”

Serine protease inhibitors suppress pancreatic endogenous proteases and modulate bacterial neutral proteases

“…Trasylol (Aprotonin) is a broad spectrum, reversible, proteinbased, non-specific inhibitor of various proteases. 31 It has been used as a pharmaceutical agent for patients during heart bypass surgery to reduce inflammatory response, 32,33 but has been recently precluded by the Food and Drug Administration (FDA) due to adverse effects on patients. [33][34][35][36] Trasylol has long been used during the islet isolation process to wash digested pancreatic tissue.…”