Nafamostat: A Comprehensive Monograph on a Multifaceted Serine Protease Inhibitor with a Uniquely Constrained Pharmacokinetic Profile

1.0 Executive Summary

Nafamostat is a synthetic, broad-spectrum serine protease inhibitor characterized by a significant dichotomy: its profound and wide-ranging biochemical potency is sharply constrained by an ultrashort biological half-life. This pharmacokinetic profile is not a limitation but rather the defining feature that dictates its clinical utility, safety profile, and the challenges associated with expanding its therapeutic applications. For over three decades, Nafamostat has been a standard-of-care agent in Japan and South Korea for the management of acute pancreatitis, disseminated intravascular coagulation (DIC), and, most notably, as a regional anticoagulant for extracorporeal circuits such as those used in hemodialysis and continuous renal replacement therapy (CRRT). In this latter role, its rapid enzymatic hydrolysis in the bloodstream is a distinct advantage, localizing its potent anticoagulant effects to the external circuit and minimizing the risk of systemic hemorrhage compared to conventional anticoagulants like heparin.