The toxicological effects of DS-7309, a glucokinase activator, on pregnancy and embryo-fetal development in rats and rabbits and maternal blood glucose levels were examined. DS-7309 was administered at 3, 10, or 100 mg/kg to rats from Days 7–17 of pregnancy or at 10, 30, or 100 mg/kg to rabbits from Days 6–18 of pregnancy. In rats, maternal hypoglycemia (approximately 50 mg/dL) was seen at 3 and 10 mg/kg, but it recovered 7 h after dosing, leading to no toxic changes. In contrast, continuous severe maternal hypoglycemia (approximately 40 mg/dL, ≥7 h), fetal eye anomalies, and decreased fetal body weight were noted at 100 mg/kg. In rabbits, no fetal anomalies were seen at 10 and 30 mg/kg where maternal blood glucose level dropped to approximately 60–90 mg/dL, but recovered by 7 h after dosing at the latest. In contrast, at 100 mg/kg, severe hypoglycemia (around 60 mg/dL) was maintained and did not recover until 24 h after dosing; it resulted in decreased fetal viability and increased fetal skeleton anomalies. These findings indicate that DS-7309 could lead to embryo-fetal toxicity in rats and rabbits, with such toxicity considered to be related to continuous severe maternal hypoglycemia.

检测了葡萄糖激酶激活剂 DS-7309 对大鼠和兔的妊娠和胚胎-胎儿发育以及母体血糖水平的毒理学影响。DS-7309 在妊娠第 7-17 天以 3、10 或 100 mg/kg 的剂量给予大鼠，或从妊娠第 6-18 天以 10、30 或 100 mg/kg 的剂量给予兔子。在大鼠中，在 3 和 10 mg/kg 时观察到母体低血糖（约 50 mg/dL），但在给药后 7 小时恢复，未导致毒性变化。相比之下，在 100 mg/kg 时注意到持续严重的母体低血糖（约 40 mg/dL，≥7 h）、胎儿眼睛异常和胎儿体重下降。在兔子中，在 10 和 30 mg/kg 时未观察到胎儿异常，而母体血糖水平降至约 60-90 mg/dL，但最迟在给药后 7 小时恢复。相反，在 100 mg/kg 时，严重低血糖（约 60 mg/dL）被维持，直到给药后 24 小时才恢复；它导致胎儿活力下降和胎儿骨骼异常增加。这些发现表明 DS-7309 可能导致大鼠和兔的胚胎-胎儿毒性，这种毒性被认为与持续的严重母体低血糖有关。