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牡荆素-4′ -O-葡萄糖苷在大鼠体内的首关效应研究
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| 篇名： | 牡荆素-4′ -O-葡萄糖苷在大鼠体内的首关效应研究 |
| TITLE： | |
| 摘要： | 目的：研究牡荆素-4′ -O-葡萄糖苷（VG）在大鼠体内的首关效应及其机制，为其新药剂型研究提供依据。方法：10只SD大鼠分为肝门静脉给药组和股静脉给药组，分别于肠系膜上静脉iv VG、股静脉灌注VG，通过测定VG在肝脏的AUC计算代谢率；15只SD大鼠分为胃灌注组、肠灌注组和肝门静脉给药组，分别于胃底、十二指肠灌注VG及肠系膜上静脉iv VG，通过测定VG在胃、肠的AUC计算代谢率；15只SD大鼠分为肠灌注组、股静脉给药组和生理盐水组，在给药前10 min，前2组大鼠灌注细胞色素P450（CYP）3A与P糖蛋白（P-gp）的底物维拉帕米注射液（60 ml/kg），生理盐水组大鼠灌注等体积生理盐水，之后按照上述方法给药，考察维拉帕米对VG肠吸收的影响。结果：VG在肝脏、胃、肠道的代谢率分别为54.9％、1.7％、91.9％；灌注维拉帕米后，肠灌注组大鼠VG的AUC表现出轻微的增加趋势。结论：肝、肠首关作用是导致VG生物利用度低的主要因素，初步判断VG是肠道CYP 3A和/或P-gp的底物。 |
| ABSTRACT： | OBJECTIVE： To investigate the first-pass effect and mechanism of vitexin-4′ -O-glucoside （VG） in rats so as to provide a basis for new drug development. METHODS： 10 SD rats were divided into a group of hepatic portal venous administration and a group of femoral venous administration， which respectively received VG iv at superior mesenteric vein and femoral vein， and then metabolic rate was calculated by finding out the AUC of VG in the rats’ livers. 15 SD rats were divided into a group of gastric infusion， a group of intestinal infusion and a group of hepatic portal venous infusion， which respectively received VG by infusion at gastric fundus and duodenum and iv at superior mesenteric vein， and then metabolic rate was calculated by finding out the AUC of VG in the rats’ stomachs and intestines. 15 SD rats were divided into a group of intestinal infusion， a group of femoral venous administration and a group of normal saline. At 10 min before administration， the former two groups were given by infusion verapamil injection （60 ml/kg）， the substrate of CYP3A and P-glycoprotein （P-gp）； and the group of normal saline were given by infusion of isometric normal saline， and then the rats were given VG as above to observe the effect of verapamil on intestinal absorption of VG. RESULTS： The metabolic rates of VG in the liver， stomach and intestine were 54.9％， 1.7％ and 91.9％ respectively. After infusion of verapamil， slight increase in AUC of VG was found in the rats in the group of intestinal infusion. CONCLUSIONS： The first-pass effects in the liver and intestine are the main factors related to the low bioavailability of VG. Based on preliminary judgment， VG is the substrate of intestinal CYP3A and/or P-gp. |
| 期刊： | 2016年第27卷第25期 |
| 作者： | 吴成举，柴纪严，张文洁 |
| AUTHORS： | WU Chengju，CHAI Jiyan，ZHANG Wenjie |
| 关键字： | 牡荆素-4′ -O-葡萄糖苷；首关效应；代谢率；CYP3A；P-糖蛋白；大鼠 |
| KEYWORDS： | Vitexin-4′ -O-glucoside； The first-pass effect； Metabolic rate； CYP3A； P-glycoprotein； Rats |
| 阅读数： | 213 次 |
| 本月下载数： | 2 次 |
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