...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Phytotherapy research: PTR >Evaluation of First-Pass Cytochrome P4503A (CYP3A) and P-glycoprotein Activities Using Felodipine and Hesperetin in Combination in Wistar Rats and Everted Rat Gut Sacs in Vitro
【24h】

Evaluation of First-Pass Cytochrome P4503A (CYP3A) and P-glycoprotein Activities Using Felodipine and Hesperetin in Combination in Wistar Rats and Everted Rat Gut Sacs in Vitro

机译：使用非洛地平和橙皮素联合评估Wistar大鼠和外翻大鼠肠囊的首过细胞色素P4503A（CYP3A）和P-糖蛋白活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The effects of hesperetin on the pharmacokinetics and the role of P-glycoprotein (P-gp) in the transport of felodipine were investigated in rats and in vitro. Felodipine was administered orally (10 mg/kg) without or with hesperetin (25, 50 and 100 mg/kg) to rats for 15 consecutive days. Blood samples were collected at different time intervals on 1~(st) day in single dose pharmacokinetic study (SDS) and on 15~(th) day in multiple dose pharmacokinetic study (MDS). The area under the plasma concentration-time curve (AUC_(0-)) and the peak plasma concentration (C_(max)) of felodipine were dose-dependently increased in SDS and MDS with hesperetin compared to control (p<0.001). The half-life (t_(1/2)) and mean residence time was longer than the control group in both studies. The role of P-gp determined using everted rat gut sacs in vitro by incubating felodipine with or without hesperetin and verapamil (typical P-gp and CYP3A4 inhibitor). The in vitro experiments revealed that the verapamil and hesperetin increased the intestinal absorption of felodipine (p<0.01). Concurrent use of hesperetin dramatically altered the pharmacokinetics of felodipine leading to an increase in systemic exposure. The likely mechanism is inhibition of CYP3A4-mediated first-pass metabolism and P-gp in the intestine and the liver.
机译：在大鼠和体外研究了橙皮素对药代动力学的影响以及P-糖蛋白（P-gp）在非洛地平转运中的作用。连续（非口服）非洛地平口服或口服橙皮素（25、50和100 mg / kg）（10 mg / kg），连续15天。在单剂量药代动力学研究（SDS）中的第1〜（st）天和在多剂量药代动力学研究（MDS）的第15〜（th）天以不同的时间间隔采集血样。与橙皮素相比，SDS和MDS中非洛地平的血浆浓度-时间曲线下面积（AUC_（0-））和峰值血浆浓度（C_（max））与对照相比呈剂量依赖性增加（p <0.001）。在两项研究中，半衰期（t_（1/2））和平均停留时间均比对照组长。 P-gp的作用是通过在体外试验中通过将非洛地平与含或不含橙皮素和维拉帕米（典型的P-gp和CYP3A4抑制剂）一起孵育来确定大鼠肠囊的体外作用。体外实验显示维拉帕米和橙皮素增加了非洛地平的肠道吸收（p <0.01）。同时使用橙皮素会极大地改变非洛地平的药代动力学，从而导致全身暴露增加。可能的机制是抑制肠和肝脏中CYP3A4介导的首过代谢和P-gp。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号