Platelet-activating factor (PAF) is a proinflammatory
lipid. It has been strongly implicated in the regulation of pancreatic exocrine secretion and in the local and systemic events which occur in
acute pancreatitis. PAF antagonists, when given as pretreatment, ameliorate the severity of experimental
acute pancreatitis by reducing serum
amylase, oxidative injury, morphological changes, polymorph infiltration, pulmonary damage, and exudative levels of PAF in blood and peritoneal fluid. The novel, potent PAF antagonist,
lexipafant, can ameliorate microvascular-induced
acute pancreatitis after induction of the disease. It also reduces
lung injury by preventing increased pulmonary capillary permeability. In a double-blind, randomized, Phase II, clinical study of
lexipafant in human
acute pancreatitis, a clinical benefit was found, as indicated by a significant reduction in an organ failure score measured during 72 h of infusion. In addition, organ failure recovered in seven of 12 severe
acute pancreatitis patients treated with
lexipafant, but recovered in only two of 11 patients given placebo. New organ failure developed in a further two patients on placebo. The results of these studies indicate that
lexipafant is a potential
therapy for the treatment of human
acute pancreatitis. A multicentre, Phase III, UK study in patients with severe
acute pancreatitis is currently underway.