Effect of New Therapeutic Agents for Pancreatitis on Serum Alpha₁-Antitrypsin and Alpha₂-Macroglobulin in Humans

Abstract

A synthetic protease inhibitor, ethyl-P-(6-guanidino hexanoyloxy) benzoate methanesulfonate (FOY), and chlorophyll-a have been proposed recently as potential therapeutic agents for acute pancreatitis. To define the mechanisms involved, serum alpha₁-antitrypsin, alpha₂-macroglobulin and amylase were determined before and after the administration of these agents in humans.
Serum alpha₁-antitrypsin and alpha₂-macroglobulin levels assayed by single radial immunodiffusion were significantly increased by intravenous injections of 100mg FOY in normal control subjects. Daily intravenous infusions of 200mg FOY for 12 days were effective in the treatment of acute pancreatitis, causing 29% increase in serum alpha₁-antitrypsin and a marked reduction in urinary isoamylase of pancreatic type as well as in serum γ-glutamyl transpeptidase. In patients with chronic pancreatitis, oral administrations of 1800mg FOY per day for 2 weeks had little effects on serum alpha₁-antitrypsin, alpha₂-macroglobulin and hourly rate of urinary amylase excretion. No significant correlation was demonstrated between serum alpha₁-antitrypsin and alpha₂-macroglobulin levels. Intravenous injections of 20mg chlorophyll-a had no effects on serum alpha₁-antitrypsin and alpha₂-macroglobulin levels in control subjects. These results indicate that the mechanisms of action of the two agents are different.