目的 研究利伐沙班的出血副作用,并对其拮抗剂对大鼠出血模型的影响进行探索.方法 大鼠ig给予不同剂量利伐沙班(0.3～30 mg/kg)1.5 h后,根据断尾法测定的出血时间、出血量,以及凝固法测定的血浆凝血酶原时间(PT),观察其出血副作用;大鼠ig给予大剂量利伐沙班(30 mg/kg)制备大鼠出血模型,尾iv人凝血酶原复合物或白眉蛇毒血凝酶,通过测定大鼠断尾出血时间、出血量以及血浆PT,观察两种药物对出血作用的拮抗效果.结果 大鼠ig给予不同剂量的利伐沙班后,出血时间、出血量、血浆PT都明显增加,与利伐沙班的剂量呈正相关;人凝血酶原复合物能够显著抑制利伐沙班所致的出血时间、出血量和血浆PT的增加,而白眉蛇毒血凝酶对上述指标无明显影响.结论 利伐沙班存在剂量相关性的出血副作用,在出血严重时,可采用人凝血酶原复合物作为拮抗剂进行治疗.
Objective To study the bleeding side effect of rivaroxaban and explore its antagonists on hemorrhage model in rats. Methods In the bleeding side effect experiment, rats were ig administered with different doses (0.3 — 30 mg/kg) of rivaroxaban. Bleeding time and blood loss were determined by tail cutting method, and plasma prothrombin time (PT) was measured by Kit method 1.5 h after administration. In the antagonist exploration experiment, hemorrhage rat model was established by ig administration of large dosage (30 mg/kg) of rivaroxaban. Human prothrombin complex and hemocoagulase were given by iv injection and their antagonistic effect was observed by measuring the bleeding time, blood loss, and plasma PT. Results Bleeding time, blood loss, and plasma PT of rats increased significantly after administration of different doses of rivaroxaban, which were positively correlated with the dose of drug. Human prothrombin complex concentrate could weaken the increase of bleeding time, blood loss, and plasma PT, while hemocoagulase had no significant effect on these indicators. Conclusion Rivaroxaban has dose-dependent side effect of bleeding, and human prothrombin complex can alleviate this side effect when severe bleeding happens.