Enright Brian P, Tornesi Belen, Weinbauer Gerhard F, Blaich Guenter
Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Birth Defects Res B Dev Reprod Toxicol. 2012 Dec;95(6):431-43. doi: 10.1002/bdrb.21034. Epub 2012 Dec 4.
ABT-874 is an anti-IL-12/23 monoclonal antibody that binds to the p40 subunit of human IL-12 and IL-23. As part of its preclinical safety assessment, studies were conducted to assess its potential effects on pre- and postnatal development in cynomolgus monkeys.
In the embryo-fetal development studies, ABT-874 was administered once weekly subcutaneously to adult female cynomolgus monkeys at doses of 0, 5, 25, or 100 mg/kg during gestation days (GD) 20 to 48. Fetuses were examined for external, visceral, and skeletal development on GD 100 or 150. In the pre- and postnatal study, ABT-874 was administered once weekly subcutaneously to adult female cynomolgus monkeys at doses of 10, 50, or 200 mg/kg from GD 20 through postpartum day 182. Infants were examined from birth up to 9 months of age for morphological and functional development. Potential effects on the infant immune system were evaluated by immunophenotyping of peripheral blood lymphocytes and by T-dependent antibody response to KLH.
There was no ABT-874-related maternal toxicity or adverse effects on fetuses or infants. ABT-874 was present in maternal and fetal serum at GD 100 and 150, and in infant serum through day 63 postbirth. ABT-874 was also present at low levels in breast milk through postpartum day 175.
Exposure of cynomolgus monkey fetuses and infants to ABT-874 had no adverse effects on embryo-fetal or postnatal development.
ABT - 874是一种抗白细胞介素12/23单克隆抗体，可与人白细胞介素12和白细胞介素23的p40亚基结合。作为其临床前安全性评估的一部分，开展了多项研究以评估其对食蟹猴产前和产后发育的潜在影响。
在胚胎 - 胎儿发育研究中，于妊娠第20至48天，每周一次皮下给予成年雌性食蟹猴0、5、25或100 mg/kg剂量的ABT - 874。在妊娠第100天或150天检查胎儿的外部、内脏和骨骼发育情况。在产前和产后研究中，从妊娠第20天至产后第182天，每周一次皮下给予成年雌性食蟹猴10、50或200 mg/kg剂量的ABT - 874。对出生至9个月大的婴儿进行形态和功能发育检查。通过外周血淋巴细胞免疫表型分析以及对钥孔戚血蓝蛋白的T细胞依赖性抗体反应评估对婴儿免疫系统的潜在影响。
未发现与ABT - 874相关的母体毒性，也未对胎儿或婴儿产生不良影响。在妊娠第100天和150天，母体和胎儿血清中存在ABT - 874，在出生后第63天婴儿血清中也存在。直至产后第175天，母乳中也存在低水平的ABT - 874。
食蟹猴胎儿和婴儿接触ABT - 874对胚胎 - 胎儿或产后发育没有不良影响。
