注射用右旋兰索拉唑家兔胚胎-胎仔发育毒性比较及伴随毒代与组织分布

发布时间：2019-06-11 03:29

【摘要】：目的:研究注射用右旋兰索拉唑对孕兔胚胎-胎仔发育的影响。方法:孕兔于妊娠第6~18天分别给予静脉注射用右旋兰索拉唑3.6,12,36 mg·kg~(-1),qd。另设兰索拉唑和左旋兰索拉唑(36 mg·kg~(-1))作为消旋和左旋对照,环磷酰胺(10 mg·kg~(-1))作为阳性对照,溶媒对照采用氯化钠注射液,第29天处死解剖。观察并记录给药前后孕兔一般症状,处死后,观察母兔生殖状态与胎仔发育情况。于首、末次给药进行伴随毒代采血,解剖时取组织样本,采用LC-MS/MS测定样本内药物浓度。结果:与溶媒对照组相比,右旋兰索拉唑中、高剂量组、消旋、左旋对照组孕兔厌食、体质量下降明显。消旋、左旋和阳性对照组给药后期个别孕兔出现流产。率转换后,右旋高剂量组、消旋、左旋对照组胎仔活胎率显著低于溶媒对照组。胎仔骨骼检查中,右旋高剂量组、消旋和左旋对照组的部分种类骨骼缺失数量,显著高于溶媒对照组。伴随毒代结果可知,右旋兰索拉唑在孕兔体内达峰迅速,代谢较快,未见蓄积。组织分布研究表明右旋兰索拉唑在母体内广泛分布,无特殊脏器亲和,易通过胎盘屏障。结论:右旋高剂量(36 mg·kg~(-1))家兔体内表现出一定的母体毒性和胚胎-胚仔发育毒性,右旋中剂量(12 mg·kg~(-1))仅表现出母体毒性。
[Abstract]:Objective: to study the effect of dextrolansoprazole for injection on embryo-fetal development in pregnant rabbits. Methods: pregnant rabbits were given dextran lansoprazole 3.6, 12, 36 mg kg~ (- 1), qd.) intravenously from the 6th to 18th day of pregnancy. Lansoprazole and L-lansoprazole (36 mg kg~ (- 1) were used as racemic and L-control, cyclophosphamide (10 mg kg~ (- 1) as positive control, and sodium chloride injection was used as solvent control. The general symptoms of pregnant rabbits before and after administration were observed and recorded. After death, the reproductive status and fetal development of female rabbits were observed. At the first and last administration, the blood samples were collected with poison, and the tissue samples were taken during anatomy, and the drug concentration in the samples was determined by LC-MS/MS. Results: compared with the solvent control group, the anorexia and body mass of the pregnant rabbits in the middle, high dose, racemic and left control groups were significantly lower than those in the solvent control group. Abortion occurred in individual pregnant rabbits in racemic, left-handed and positive control groups at the later stage of administration. After conversion, the live fetal rate of right-handed high dose group, racemic and left-handed control group was significantly lower than that of solvent control group. In fetal bone examination, the number of bone deletions in right-handed high dose group, racemic and left-handed control group was significantly higher than that in solvent control group. The results of toxicity showed that dextran lansoprazole reached the peak rapidly, metabolized quickly and did not accumulate in pregnant rabbits. Tissue distribution studies showed that dextrolansoprazole was widely distributed in the mother and had no special organ affinity and was easy to pass through the placental barrier. Conclusion: right-handed high dose (36 mg kg~ (- 1) rabbits show certain maternal toxicity and embryo-embryo development toxicity, while right-handed medium dose (12 mg kg~ (- 1) only shows maternal toxicity.
【作者单位】：南京工业大学;江苏省药物研究所;
【基金】：江苏省政策引导类计划产学研合作项目(编号:BY2015005-04)
【分类号】：R965

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