Amrinone, a phosphodiesterase III inhibitor, and arachidonic acid metabolism in humans

Amrinone-a phosphodiesterase III inhibitor-is used in the treatment of acut e heart failure. In addition to its hemodynamic effects, amrinone has been shown to inhibit thromboxane synthesis in vitro. We investigated the effect s of amrinone on thromboxane, prostaglandin, and leukotriene synthesis in h umans. Eight healthy male volunteers took part in this single-blind study i n which either amrinone (a 1.5 mg/kg bolus in 30 min and after that 10 mu g /kg/min for 1 h 30 min) or placebo (0.9% NaCl) were infused. Amrinone infus ion increased systolic blood pressure but had no significant effect on dias tolic blood pressure or heart rate. Amrinone did not modulate thromboxane B -2 synthesis stimulated by either spontaneous clotting or calcium-ionophore A23187 in whole blood. Amrinone had no effects on prostaglandin E-2 or leu kotriene E-4 production in A23187-stimulated whole blood, nor did it affect urinary excretion of 11-dehydrothromboxane B-2 or 2,3-dinor-6-keto-prostag landin F-1 alpha, the index metabolites of thromboxane A(2) and prostacycli n productions, respectively. We conclude that amrinone has no effects on ei cosanoid production in humans at: the dose level used in this study, and th at the hemodynamic effects noticed are not mediated via cyclooxygenase or l ipoxygenase products of arachidonic acid metabolism.