Changes in plasma and urinary 11-dehydrothromboxane B2 in healthy subjects produced by oral CS-518, a novel thromboxane synthase inhibitor

Abstract

When 50 mg CS-518, a novel thromboxane (TX) A2 synthase inhibitor, was orally administered to healthy male volunteers, the plasma concentration of CS-518 peaked after 0.5 h and then decreased with a half-life of 0.44 h. There was no significant change in the plasma concentration of circulating TXB2, whereas that of circulating 11-dehydrothromboxane B2 (11-dhTXB2), an enzymatic metabolite of TXB2, was significantly decreased from 0.5 h to 24 h after administration; the maximal decrease to about 25% of the pre-dose value was found at 6 h. After CS-518 100 mg b.d. for 4.5 days, plasma 11-dhTXB2 was suppressed to the same extent as after the single dose of 50 mg from 6 h after the initial dose throughout the administration period. The urinary excretion of 11-dhTXB2 corrected for the creatinine level was significantly decreased by 70-84% throughout the treatment. These results suggest that CS-518 causes long-lasting inhibition of TXA2 synthase despite its rapid elimination from plasma, and that circulating 11-dhTXB2 in plasma and its urinary excretion can serve as a quantitative index of TXA2 synthase inhibition in vivo by CS-518.

Effect of precision antiplatelet therapy based on CYP2C19/11-dhTxB2 variability in prognosis of ischemic stroke/TIA patients: study protocol for a multicenter randomized controlled trial

“…A genetically tailored antiplatelet therapy within the study population is needed as previous studies have found a high prevalence of clopidogrel resistance in Asian populations [13,14] . In recent years, the most common CYP2C19*2, *3 mutation sites in the human cytochrome P450 allele have attracted much attention [15][16][17][18] . Aspirin is widely used in secondary prevention of stroke.…”