In vitro inhibition of phospholipase A2 by gabexate mesilate, camostate, and aprotinine

Abstract

Gabexate mesilate (FOY, ethyl-p-(6-guanidino-hexanoyl-oxy)-benzoate-methansulfonate), camostate (N,N-dimethyl-carb-amoylmethyl-4-(guanidinobenzoyloxy)-phenyl-acetate) methansulfonate and aprotinine (Trasylol) were tested for possible inhibition of phospholipase A₂. Gabexate mesilate at a concentration of 5×10⁻⁴ 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.