Gabexate mesilate and camostate: new inhibitors of phospholipase A2 and their influence on the alpha-amylase activity in serum of patients with acute pancreatitis.
The new synthetic polyvalent protease inhibitors gabexate mesilate (ethyl-p[6-guanidinohexanoyloxy]-benzoate methansulfonate) and camostate (N,N-dimethylcarbamoylmethyl-4-[4-guanidinobenzoyloxy]-phenylacetate methansulfonate) were tested for possible inhibition of phospholipase A2 activity. In a pilot study, we treated 17 patients suffering from acute pancreatitis with continuous intravenous administration of gabexate mesilate, 450 mg/d. The results were compared with a placebo group (same standard therapy) of 21 patients suffering from acute pancreatitis. In vitro experiments showed that, at concentrations between 10(-4) and 5 X 10(-4) mol/L (depending on the enzyme assay employed) for gabexate mesilate and between 10(-3) and 5 X 10(-4) mol/L for camostate, a 50% reduction in phospholipase A2 activity was effected. Comparing the two groups of acute pancreatitis patients after 6 days of treatment with gabexate mesilate, we observed a statistically significantly lower alpha-amylase activity in the serum of treated patients compared with the placebo group.
J
J
Freise
F W
FW
Schmidt
P
P
Magerstedt
K
K
Schmid
D000208:Acute Disease; D007611:Aprotinin / Q000627:therapeutic use; D004952:Esters; D016670:Gabexate; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D010195:Pancreatitis / Q000188:drug therapy* / Q000201:enzymology; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D000516:alpha-Amylases / Q000097:blood*
D004952:Esters; D006146:Guanidines; C034532:camostat; D016670:Gabexate; D007611:Aprotinin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D000516:alpha-Amylases