Yarrington J T, Kociba G J, Gibson J P
Toxicology Department, Marion Merrell Dow, Inc., Cincinnati, OH 45215.
Toxicol Lett. 1991 Apr;56(1-2):127-36. doi: 10.1016/0378-4274(91)90098-q.
Two-week oral administration of MDL-19,660, a triazole antidepressant compound, resulted in a dose-related thrombocytopenia in rats given 40-360 mg/kg/d and dogs treated with 5-50 mg/kg/d. Consumptive loss of platelets was not apparent since splenomegaly, hemorrhage, microscopic thrombi or prolonged coagulation times (prothrombin and activated partial thromboplastin) were not observed. Platelet production did not appear to be impaired since megakaryocytes in the bone marrow of treated animals were similar in number or slightly increased compared to control animals. Although the pathogenesis of this thrombocytopenia is presently unknown, intravascular destruction by immune mechanisms or direct drug-related effects seems most likely.
给予大鼠40 - 360毫克/千克/天、犬5 - 50毫克/千克/天剂量的三唑类抗抑郁化合物MDL - 19,660进行为期两周的口服给药后,出现了剂量相关的血小板减少症。由于未观察到脾肿大、出血、微血栓或凝血时间延长(凝血酶原时间和活化部分凝血活酶时间),血小板的消耗性损失并不明显。治疗动物骨髓中的巨核细胞数量与对照动物相似或略有增加,因此血小板生成似乎未受损害。尽管目前尚不清楚这种血小板减少症的发病机制,但免疫机制介导的血管内破坏或直接的药物相关效应似乎最为可能。