抗血栓药的发展及替格瑞洛的早期研究.ppt

BRILIQUE: Does Not Require Hepatic Metabolism For Activation Reference Schomig A. 替格瑞洛 — is there need for a new player in the antiplatelet-therapy field? N Engl J Med. 2009;361:1108–1111. 替格瑞洛 is rapidly absorbed following oral administration[Husted 2009:B; EMEA Label:A] 替格瑞洛 is metabolized primarily via cytochrome P450 3A enzymes and has one known active metabolite, ARC124910XX, that is present in blood at approximately one-third of the concentration of the parent drug[Teng 2010:A; EMEA Label:B] Although this metabolite has potency in inhibiting the P2Y12 receptor equivalent to that of the parent compound, metabolic activation is not a requirement for IPA to occur In 6 受试者 receiving a single oral dose of 14Cticagrelor, average total recovery of radioactive dose was 84.3%, consisting of 26.5% in urine and 57.8% in feces[Husted 2009:F] 替格瑞洛 and its active metabolite, AR-C124910XX, constituted the major components identified in feces, plasma, and less than 1% of components in urine Absorption of 替格瑞洛 is rapid (median time to peak plasma concentration [tmax] of 1.3-2 hours), as is the formation of its main (active) metabolite, AR-C124910XX (tmax 1.5-3 hours)[Teng 2010:B] The mean terminal-phase half-life is approximately 7 to 8.5 hours for 替格瑞洛 and 8.5 to 10 hours for AR-C124910XX[Teng 2010:B,C; EMEA Label D,E] AR-C124910XX exposure is approximately one-third that of 替格瑞洛 Exposure to 替格瑞洛 is slightly higher (approximately 1.25-fold) following administration with food, with exposure to AR-C124910XX not appearing to be affected, suggesting it can be administered with or without food[Butler 2008:B; EMEA Label:E] Husted S, et al. Cardio Ther. 2009;27:259-274. Butler K et al, Can J Clin Pharmacol. 2008;15:e684-e685 [Abstract 562]. Teng R. Eur J Clin Pharmacol. 2010;66:487-496. Clinical Pharmacology: BRILIQUE and 氯吡格雷 References Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of 替格瑞洛 versus 氯吡格