Embryo-fetal development toxicity of carenoprazan hydrochloride
10.11665/j.issn.1000-5048.20180614
- VernacularTitle:盐酸柯诺拉赞的胚胎-胎仔发育毒性
- Author:
Ming CAI
1
;
Bin SHU
;
Qing SHAO
;
Yanjuan YUAN
;
Yutang ZHANG
;
Hongqun QIAO
;
Jing LIU
Author Information
1. 江苏省药物研究所江苏省药物安全性评价中心
- Publication Type:Journal Article
- Keywords:
carenoprazan hydrochloride;
development toxicity;
toxicokinetics;
placental barrier
- From:
Journal of China Pharmaceutical University
2018;49(6):725-730
- CountryChina
- Language:Chinese
-
Abstract:
Carenoprazan has the similar structure and mechanism with the potassium-competitive blocker vonoprazan. Howerver, its safety during the pregnancy remains uncertain. To study the embryo-fetal development toxicity and toxicokinetics of carenoprazan hydrochloride via oral administration, time-mated Sprague-Dawley rats were divided into 5 groups, treated with normal saline, cyclophosphamide for injection(3. 8 mg/kg), and carenoprazan hydrochloride(20, 60, 200 mg/kg), respectively. Administrated orally from gestation day(GD)6 - 15. At the termination(GD 20), pregnant dams were sacrificed, and concentrations of carenoprazan hydrochloride as well as its metabolite in plasma and issues of both maternal and fetus were examined. As a result, the body weight gain of maternal in both high(200 mg/kg)and medium(60 mg/kg)dose as well as the food consumption of high-dose were decreased during GD 10-16. At the high dose group, decrease of crown rump length of fetuses were significant. Also, skeletal malformation/variations of fetus increased obviously at both high- and medium- dosage. The toxcicokinetics of carenoprazan hydrochloride are linear after single treatment between 20-200 mg/kg. The placental barrier was penetrated by carenoprazan hydrochloride and metabolite, and the distribution of metabolite in organs were similar in both maternal and fetus, with the highest concentration in livers. Therefore might resulted in the development toxicity. The No Observed Adverse Effect Level(NOAEL)of carenoprazan hydrochloride for both maternal and fetal was 20 mg/kg.
