Evaluation of developmental toxicity of propylthiouracil and methimazole.
Evaluation of developmental toxicity of propylthiouracil and methimazole.
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丙基硫氧嘧啶和他巴唑的发育毒性评价。
DOI：
10.1002/bdrb.21113
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Rivkees,ScottA
中科院分区：
文献类型：
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作者：
Mallela,MuraliK;Strobl,Marie;Poulsen,RyanR;Wendler,ChristopherC;Booth,CarmenJ;Rivkees,ScottA
背景丙硫氧嘧啶(PTU)和他巴唑(MMI)是用于治疗甲状腺功能亢进症的抗甲状腺药物。尽管PTU和MMI在怀孕期间被广泛使用，但关于这些药物的致畸潜力的临床数据和动物数据较少。方法我们评估了宫内暴露于PTU或MMI对小鼠和大鼠的致畸作用。首先，从妊娠第6天到第16天，每天给予妊娠C57BL/6小鼠PTU(10或100 mg/kg)、MMI(2或20 mg/kg)或赋形剂，观察GD18胎鼠的大体和组织病理学改变。妊娠SD大鼠每日分别给予PTU(50 mg/kg或100 mg/kg)、MMI(10 mg/kg或20 mg/kg)或GD20~19d的赋形剂治疗，然后在GD20进行大体和组织病理学检查。结果PTU和MMI处理的小鼠在GD18未观察到明显的组织病理学异常和外部大体畸形，对胎盘重量、胎盘大小、吸收率和胎儿体重也无不良影响。PTU(50 mg/kg和100 mg/kg)和MMI(10 mg/kg)可使胎鼠的头臀长度缩短，但未观察到外部大体畸形或组织病理学异常。结论在妊娠期间长期给予大剂量PTU或MMI的小鼠和大鼠未观察到大体外部畸形或组织病理畸形。
BACKGROUNDPropylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest clinical data and less animal data are available on the teratogenic potential of these drugs.METHODSWe evaluated the teratogenicity of in utero exposure to PTU or MMI in mice and rats. First, pregnant C57Bl/6 mice were treated daily with PTU (10 or 100 mg/kg), MMI (2 or 20 mg/kg), or vehicle from gestation day (GD) 6 to 16. GD 18 fetuses were evaluated for gross and histopathological abnormalities. Next, pregnant Sprague‐Dawley rats were treated daily with PTU (50 or 100 mg/kg), MMI (10 or 20 mg/kg), or vehicle from GD 6 to 19, followed by evaluation for gross and histopathological abnormalities at GD 20.RESULTSIn mice treated with PTU or MMI, no significant histopathological abnormalities or external gross malformations, and no adverse effects on placental weight, litter size, resorption rates, or fetal weight were observed at GD 18. In rats, no adverse effects on litter size, placental weights, or maternal body weights were observed with either PTU or MMI treatment. PTU treatment (50 and 100 mg/kg) and MMI (10 mg/kg) treatment resulted in a decrease in crown‐rump length in rat fetuses but no external gross malformations or histopathological abnormalities were observed.CONCLUSIONWe did not observe either gross external malformations or histopathological malformations in mice or rats treated long‐term with high doses of PTU or MMI during pregnancy