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首页> 外文期刊>Journal of applied toxicology >Embryo–fetal toxicity assessment of vonoprazan in rats and rabbits
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Embryo–fetal toxicity assessment of vonoprazan in rats and rabbits

机译：大鼠和兔Vonoprazan的胚胎胎儿毒性评估

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Abstract Vonoprazan is a new potassium‐competitive acid blocker to treat acid‐related diseases. However, its safety during pregnancy is unclear. The aim of the study was to investigate the potential reproductive toxicity on the embryo–fetal development of vonoprazan. Vonoprazan acetate was administered by intravenous injection to pregnant rats (0, 2, 6 and 20?mg?kg –1 day –1 ) and rabbits (0, 1.2, 3.6 and 12?mg?kg –1 day –1 ) during the organogenetic period (gestation day 6–15 [rats] and 6–18 [rabbits]). Maternal reproductive endpoints were evaluated, together with effects on fetal growth and morphological development. In rats, no treatment‐related effects were found in the highest dose group (20?mg?kg –1 ) and the maternal plasma exposure was ≥50‐fold the expected clinical human exposure. However, in rabbits, dose‐related clinical signs (soft or liquid feces) occurred in the 12?mg?kg –1 group, which was regarded as a maternal toxicity. Besides, decreased maternal weight gain also was considered as a minimal maternal toxicity. At 12?mg?kg –1 , delayed fetal ossification was found as evidence of embryo–fetal growth retardation, which was related to decreased fetal and placental weights. There was no maternal and developmental toxicity in the 1.2 and 3.6?mg?kg –1 groups. Thus, the no‐observed‐adverse‐effect levels of vonoprazan acetate in rabbits are considered 3.6?mg?kg –1 day –1 , which produced plasma exposure that was about 18‐fold human clinical exposure.
机译：摘要vonoprazan是一种新的钾竞争性酸障碍物，用于治疗酸相关的疾病。然而，怀孕期间的安全性尚不清楚。该研究的目的是探讨潜在的雌醛胎儿发育潜在的生殖毒性。醋酸醋酸甲醇通过静脉注射给孕腺预热（0,2,6和20×mg？kg -1天-1）和兔（0,1.2,3.6和12？mg？kg -1天-1）给药有机氢时期（妊娠第6-15天[大鼠]和6-18 [兔子]）。评估母体生殖终点，以及对胎儿生长和形态学发育的影响。在大鼠中，在最高剂量组（20μm≤kg-1）中没有发现治疗相关的效果，并且母体血浆暴露≥50倍的预期临床人暴露。然而，在兔子中，在12？Mg -11组中发生剂量相关的临床符号（软或液体粪便），被认为是母体毒性。此外，母体体重增加降低也被认为是最小的母体毒性。在12？毫克kg -1时，发现延迟胎儿骨化作为胚胎胎儿生长迟缓的证据，​​这与胎儿和胎盘重量降低有关。 1.2和3.6毫克的母亲和发育毒性没有？kg -1组。因此，兔醋酸甲丙烷的无观察到的不良效应水平被认为是3.6？Mg？kg -1天-1，其产生约18倍的人类临床暴露的血浆暴露。

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