Amrinone, a phosphodiesterase III inhibitor, and arachidonic acid metabolism in humans.
Amrinone-a phosphodiesterase III inhibitor-is used in the treatment of acute heart failure. In addition to its hemodynamic effects, amrinone has been shown to inhibit thromboxane synthesis in vitro. We investigated the effects of amrinone on thromboxane, prostaglandin, and leukotriene synthesis in humans. Eight healthy male volunteers took part in this single-blind study in which either amrinone (a 1.5-mg/kg bolus in 30 min and after that 10 microg/kg/min for 1 h 30 min) or placebo (0.9% NaCl) were infused. Amrinone infusion increased systolic blood pressure but had no significant effect on diastolic blood pressure or heart rate. Amrinone did not modulate thromboxane B2 synthesis stimulated by either spontaneous clotting or calcium-ionophore A23187 in whole blood. Amrinone had no effects on prostaglandin E2 or leukotriene E4 production in A23187-stimulated whole blood, nor did it affect urinary excretion of 11-dehydrothromboxane B2 or 2,3-dinor-6-keto-prostaglandin F1alpha, the index metabolites of thromboxane A2 and prostacyclin productions, respectively. We conclude that amrinone has no effects on eicosanoid production in humans at the dose level used in this study, and that the hemodynamic effects noticed are not mediated via cyclooxygenase or lipoxygenase products of arachidonic acid metabolism.
Kerttula
T
T
Department of Clinical Chemistry, Tampere University Hospital, University of Tampere, Finland.
Alanko
J
J
Seppälä
E
E
Riutta
A
A
Mucha
I
I
Sievi
E
E
Kaukinen
S
S
D000328:Adult; D000676:Amrinone / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism*; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism / Q000652:urine; D013931:Thromboxanes / Q000378:metabolism / Q000652:urine
D001095:Arachidonic Acids; D015289:Leukotrienes; D010726:Phosphodiesterase Inhibitors; D011453:Prostaglandins; D013931:Thromboxanes; D000676:Amrinone