Differential effects of dazoxiben, a selective thromboxane-synthase inhibitor, on platelet and renal prostaglandin-endoperoxide metabolism.

摘要: Pharmacologic inhibition of thromboxane (TX) synthase can result in redirection prostaglandin (PG) endoperoxide metabolism, possibly affecting platelet, vascular and renal function. This study explores the vitro, ex vivo effects dazoxiben, an orally active TX-synthase inhibitor, on platelet TXB2 production associated changes PG-endoperoxide metabolism. Dazoxiben inhibits clotting human whole blood with IC50 0.3 micrograms/ml causes parallel enhancement PGE2 greater than PGF2 alpha 6-keto-PGF1 production. Similar metabolism is observed vivo, after oral administration 1.5 3.0 mg/kg to six healthy volunteers. Plasma ranges between less 4 8 pg/ml during first 3 h. Urinary excretion, a reflection TXA2 production, significantly reduced by 30% no evidence In vitro rat kidney glomeruli requires higher dazoxiben concentration (IC50 = 1.60 micrograms/ml) 0.32 not PGE2, These results demonstrate quantitatively qualitatively diverse different TXA2-producing cells suggest possibility developing tissue-selective inhibitors.