胡椒碱和奥美拉唑对达卡他韦兔肠局部吸收的影响

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Shimaa M. Ashmawy, Dina A. Eltahan, Mohamed A. Osman, Ebtessam A. Essa
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引用次数: 0

摘要

本研究评估了Daclatasvir的部位依赖性肠吸收,并利用兔原位肠灌注技术研究了胡椒碱和奥美拉唑对这种吸收的影响。Daclatasvir在十二指肠、空肠、回肠和结肠四个肠段进行肠吸收评估。通过检测解剖部位监测与奥美拉唑共灌注的效果。研究了p糖蛋白(P-gp)抑制剂胡椒碱对空肠和回肠吸收Daclatasvir的影响。结果表明,Daclatasvir在家兔小肠和大肠吸收不完全。单位长度吸收清除率(PeA/L)与部位有关,被列为结肠>十二指肠祝辞空肠祝辞回肠。这一等级与肠道P-gp含量的等级相反,提示P-gp可能受到影响。奥美拉唑共灌注增加了PeA/L,这也证明了Daclatasvir在小肠和大肠段的L95%的降低。胡椒碱的存在显著增强了空肠和回肠对Daclatasvir的吸收。Daclatasvir表现出部位依赖性肠吸收,提示其受P-gp外排的影响。这种作用被胡椒碱所抑制。Daclatasvir与奥美拉唑合用可促进肠道吸收,这一现象需要扩展到人体药代动力学研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Influence of piperine and omeprazole on the regional absorption of Daclatasvir from rabbit intestine

Influence of piperine and omeprazole on the regional absorption of Daclatasvir from rabbit intestine

The study assessed the site dependent intestinal absorption of Daclatasvir and investigated the effects of piperine and omeprazole on such absorption utilizing in situ rabbit intestinal perfusion technique. The intestinal absorption of Daclatasvir was assessed in four segments: duodenum, jejunum, ileum, and colon. The effect of co-perfusion with omeprazole was monitored through the tested anatomical sites. The effect of piperine, a P-glycoprotein (P-gp) inhibitor on Daclatasvir absorption from jejunum and ileum was tested. The results showed that Daclatasvir was incompletely absorbed from the rabbit small and large intestine. The absorptive clearance per unit length (PeA/L) was site dependent and was ranked as colon > duodenum > jejunum > ileum. This rank is the opposite of the rank of P-gp intestinal content suggesting possible influence for P-gp. Co-perfusion with omeprazole increased PeA/L and this was evidenced also with reduced the L95% of Daclatasvir from both small and large intestinal segments. Significant enhancement in Daclatasvir absorption through jejunum and ileum was shown in presence of piperine. Daclatasvir showed site dependent intestinal absorption in a manner suggesting its affection by P-gp efflux. This effect was inhibited by piperine. Co-administration of Daclatasvir with omeprazole can enhance intestinal absorption a phenomenon which requires extension to human pharmacokinetic investigation.

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来源期刊
CiteScore
3.60
自引率
0.00%
发文量
35
审稿时长
6-12 weeks
期刊介绍: Biopharmaceutics & Drug Dispositionpublishes original review articles, short communications, and reports in biopharmaceutics, drug disposition, pharmacokinetics and pharmacodynamics, especially those that have a direct relation to the drug discovery/development and the therapeutic use of drugs. These includes: - animal and human pharmacological studies that focus on therapeutic response. pharmacodynamics, and toxicity related to plasma and tissue concentrations of drugs and their metabolites, - in vitro and in vivo drug absorption, distribution, metabolism, transport, and excretion studies that facilitate investigations related to the use of drugs in man - studies on membrane transport and enzymes, including their regulation and the impact of pharmacogenomics on drug absorption and disposition, - simulation and modeling in drug discovery and development - theoretical treatises - includes themed issues and reviews and exclude manuscripts on - bioavailability studies reporting only on simple PK parameters such as Cmax, tmax and t1/2 without mechanistic interpretation - analytical methods
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