Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, Egypt.
J Pharm Pharmacol. 2019 Mar;71(3):362-370. doi: 10.1111/jphp.13036. Epub 2018 Oct 26.
The aim of this research was to assess regional difference in the intestinal absorption of ranitidine HCl as an indicator for the potential effect of P-glycoprotein (P-gp) efflux transporters.
In situ rabbit intestinal perfusion was used to investigate absorption of ranitidine HCl, a substrate for P-gp efflux from duodenum, jejunum, ileum and colon. This was conducted both in the presence and absence of piperine as P-gp inhibitor.
Ranitidine HCl was incompletely absorbed from rabbit intestine. The length normalized absorptive clearance (PeA/L) of ranitidine HCl was ranked as colon > duodenum > jejunum > ileum. This is the reverse order of the magnitude of P-gp expression. Coperfusion of piperine with ranitidine HCl significantly increased the PeA/L of ranitidine HCl from jejunum and ileum with no significant change on the absorption from duodenum and colon. This was confirmed by significant reduction in the length required for complete ranitidine HCl absorption from jejunum and ileum in presence piperine.
The results indicate that P-gp transporters play a major role in determining regional difference in intestinal absorption of ranitidine HCl. Thus, the regional absorption of drugs may be taken as an indirect indication for the role of P-gp in intestinal absorption.
本研究旨在评估盐酸雷尼替丁的肠道吸收的区域差异，以评估 P-糖蛋白（P-gp）外排转运体的潜在影响。
采用原位兔肠灌流法研究了 P-gp 外排底物盐酸雷尼替丁在十二指肠、空肠、回肠和结肠中的吸收情况。同时研究了胡椒碱作为 P-gp 抑制剂对盐酸雷尼替丁吸收的影响。
盐酸雷尼替丁在兔肠中吸收不完全。盐酸雷尼替丁的长度归一化吸收清除率（PeA/L）排序为结肠>十二指肠>空肠>回肠。这与 P-gp 表达量的大小顺序相反。胡椒碱与盐酸雷尼替丁共灌流显著增加了空肠和回肠中盐酸雷尼替丁的 PeA/L，而对十二指肠和结肠的吸收没有显著影响。在存在胡椒碱的情况下，从空肠和回肠完全吸收盐酸雷尼替丁所需的长度显著减少，证实了这一点。
结果表明，P-gp 转运体在决定盐酸雷尼替丁的肠道吸收的区域差异方面起着主要作用。因此，药物的区域吸收可以作为 P-gp 在肠道吸收中的作用的间接指示。
