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• W1969072425 startingPage "1025" @default.
• W1969072425 abstract "Background In vitro studies have demonstrated that ticagrelor, an oral antiplatelet agent, is a substrate, activator, and inhibitor of cytochrome P450 (CYP) 3A. Thus, potential CYP3A-mediated drug–drug interactions may occur. Objectives The goal of this article was to report study results on the effect of ticagrelor on the pharmacokinetics of oral midazolam (oral midazolam study) and oral versus intravenous (IV) midazolam (oral/IV midazolam study). Secondary objectives included assessing the effect of midazolam on ticagrelor pharmacokinetic parameters, and the safety and tolerability of ticagrelor/midazolam coadministration. Methods Two randomized crossover studies were conducted in healthy volunteers (n = 28 in each) with ticagrelor and midazolam. In the first study, volunteers received oral ticagrelor (400 mg daily) or placebo for 6 days, then oral midazolam (7.5 mg). The second study regimen was a single dose of ticagrelor 270 mg, then ticagrelor 180 mg BID for 6 days with a single oral (7.5 mg) or IV (2.5 mg) dose of midazolam. Results After oral midazolam administration, ticagrelor significantly reduced the AUC0–∞ of midazolam (30%–32%) and 4-hydroxymidazolam (42%–47%) but not 1-hydroxymidazolam. After administration of IV midazolam, ticagrelor reduced the AUC0–∞ of midazolam (12%) and 4-hydroxymidazolam (23%) but not 1-hydroxymidazolam. Conclusions These results indicate that ticagrelor can weakly activate the metabolism of midazolam to its major 1′-hydroxy metabolite, and at the same time, seems to weakly inhibit midazolam 4′-hydroxylation. Furthermore, ticagrelor affects both hepatic and intestinal CYP3A activity." @default.
• W1969072425 created "2016-06-24" @default.
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• W1969072425 creator A5040173544 @default.
• W1969072425 date "2013-07-01" @default.
• W1969072425 modified "2023-09-26" @default.
• W1969072425 title "The Effect of Ticagrelor on the Metabolism of Midazolam in Healthy Volunteers" @default.
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• W1969072425 doi "https://doi.org/10.1016/j.clinthera.2013.06.003" @default.
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