Modulation of arachidonate metabolite generation in human blood by oral defibrotide.
Acute intravenous administration in man of defibrotide (CAS 83712-60-1), a polynucleotide derivative, induces increase of 6-keto-PGF1 alpha and PGE2 production from appropriately stimulated whole blood. In the present study including acute and chronic experiments, defibrotide (Prociclide) orally administered during two weeks to healthy volunteers significantly increased the amounts of 6-keto-PGF1 alpha generated after appropriate stimulation in whole blood and in a neutrophilic leukocytes-platelet suspension. Similar effects were observed for PGE2, while TXB2 production was unchanged. Furthermore, platelet aggregation induced by calcium ionophore A23817 and production of leukotriene B4 from whole blood and isolated polymorphonuclear neutrophils were inhibited. The observed results suggest that defibrotide is biochemically active also by the oral route although the pharmacological and clinical value of the observed changes needs to be assessed.
Biagi
G
G
Chair of Medical Pathophysiology, University Hospital S. Orsola, Bologna, Italy.
Legnani
C
C
Rodorigo
G
G
Coccheri
S
S
D000328:Adult; D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D000001:Calcimycin / Q000494:pharmacology; D004311:Double-Blind Method; D015777:Eicosanoids / Q000097:blood; D006801:Humans; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D011453:Prostaglandins / Q000097:blood
D000933:Antifibrinolytic Agents; D001095:Arachidonic Acids; D015777:Eicosanoids; D010975:Platelet Aggregation Inhibitors; D011089:Polydeoxyribonucleotides; D011453:Prostaglandins; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; C036901:defibrotide