In vitro inhibition of phospholipase A2 by gabexate mesilate, camostate, and aprotinine.
Gabexate mesilate (FOY, ethyl-p-(6-guanidino-hexanoyl-oxy)-benzoate-methansulfonate), camostate (N,N-dimethyl-carb-amoylmethyl-4-(guanidinobenzoyloxy)-phenyl-acet ate) methansulfonate and aprotinine (Trasylol) were tested for possible inhibition of phospholipase A2. Gabexate mesilate at a concentration of 5 x 10(-4) mol/l and camostate at a concentration of 10(-3) mol/l caused a 50% reduction in enzyme activity. There was almost no inhibition by aprotinine at clinical doses; 40 million KIU/l were necessary to reduce phospholipase A2 activity by 20%. From the therapeutic dose (4,000 mg/day per i.v. infusion) and the half-life of gabexate mesilate in blood circulation (1 min) it can be calculated that the in vitro concentration of gabexate mesilate is only 10(-6) to 10(-7) mol/l. Under these conditions gabexate mesilate cannot diminish the in vivo enzyme activity of phospholipase A2.
Freise
J
J
Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover.
Wittenberg
H
H
Magerstedt
P
P
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004952:Esters; D016670:Gabexate; D006146:Guanidines / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D013552:Swine
D004952:Esters; D006146:Guanidines; C034532:camostat; D016670:Gabexate; D007611:Aprotinin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2