生物活性

• 描述P2Y(12) plays an important role in regulating platelet aggregation and function. This receptor is the primary target of thienopyridine antiplatelet agents, the active metabolites of which bind irreversibly to the receptor, and of newer agents that can directly and reversibly modulate receptor activity. Ticagrelor (AZD6140) is a reversible oral P2Y12 receptor antagonist for the treatment of platelet aggregation, with a K_i value of 2 nM. Ticagrelor moderately inhibited CYP2C9 activity in human liver microbodies, while it had almost no inhibitory activity for CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2D6, and CYP2E1. In human liver microsomes, ticagrelor inhibited 4-hydroxylation of midazolam and activated 1-hydroxylation of midazolam. It was assessed in fresh human hepatocytes that ticagrelor was not an inducer of CYP1A2 or CYP3A4. B16-F10 cells exhibited decreased interaction with platelets from ticagrelor-treated mice compared to saline-treated mice. In B16-F10 melanoma intravenous and intrasplenic metastasis models, mice treated with a clinical dose of ticagrelor (10 mg/kg) exhibited marked reductions in lung (84%) and liver (86%) metastases. Furthermore, ticagrelor treatment improved survival compared to saline-treated animals. A similar effect was observed in a 4T1 breast cancer model, with reductions in lung (55%) and bone marrow (87%) metastases following ticagrelor treatment. Single oral administration of ticagrelor (1-10 mg/kg) caused dose-related inhibitory effect on platelet aggregation. Ticagrelor, at the highest dose (10 mg/kg) significantly inhibited platelet aggregation at 1h after dosing and the peak inhibition was observed at 4h after dosing.

• 动物研究
  剂量	Rat: 10 mg/kg - 30 mg/kg[3] (i.p.); 1 mg/kg - 30 mg/kg[4] (p.o.) Mice: 3 mg/kg[5] (p.o.)
  给药途径	i.p., p.o.
  动物药代数据	Animal Rats[6] Dose 10 mg/kg Administration p.o. AUC0→24h 1431.30 ng·h/ml T1/2 2.94 h Tmax 1.40 h Cmax 296.53 ng/ml AUC0→∞ 1479.91 ng·h/ml