Hagopian G S, Hoover D M, Markham J K
Lilly Research Laboratories, Toxicology Division, Greenfield, Indiana 46140.
Fundam Appl Toxicol. 1988 May;10(4):672-81. doi: 10.1016/0272-0590(88)90194-7.
The teratogenic potential of the leukotriene antagonist LY171883, a novel antiasthma agent, was investigated in CD rats and Dutch Belted rabbits. Mated female rats were dosed with 0, 10, 65, or 425 mg/kg/day on gestation days 6 through 15 and killed on gestation day 20. Mated female rabbits were dosed with 0, 20, 65, or 200 mg/kg/day on gestation days 6 through 18 and killed on gestation day 28. Maternal toxicity was indicated at 425 mg/kg in rats and 200 mg/kg in rabbits by depressed body weight gain and food consumption. In the rabbit study four abortions occurred at 200 mg/kg, most likely secondarily to maternal toxicity. LY171883 did not cause embryo/fetal toxicity or teratogenicity in rats or rabbits at doses up to and including those that were maternally toxic.
新型抗哮喘药物白三烯拮抗剂LY171883的致畸潜力在CD大鼠和荷兰带兔中进行了研究。交配后的雌性大鼠在妊娠第6至15天给予0、10、65或425mg/kg/天的剂量，并在妊娠第20天处死。交配后的雌性兔在妊娠第6至18天给予0、20、65或200mg/kg/天的剂量，并在妊娠第28天处死。大鼠中425mg/kg和兔中200mg/kg时出现母体毒性，表现为体重增加和食物消耗减少。在兔的研究中，200mg/kg时发生了4次流产，很可能继发于母体毒性。在高达并包括产生母体毒性的剂量下，LY171883在大鼠或兔中均未引起胚胎/胎儿毒性或致畸性。
