Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, Egypt.
Biopharm Drug Dispos. 2022 Feb;43(1):33-44. doi: 10.1002/bdd.2308. Epub 2022 Jan 28.
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.
该研究评估了达卡他韦在肠道不同部位的吸收情况，并利用原位兔肠灌流技术研究了胡椒碱和奥美拉唑对其吸收的影响。达卡他韦的肠吸收在四个部位进行评估：十二指肠、空肠、回肠和结肠。通过测试解剖部位监测与奥美拉唑共灌注的影响。测试了 P 糖蛋白（P-gp）抑制剂胡椒碱对空肠和回肠中达卡他韦吸收的影响。结果表明，达卡他韦从兔小肠和大肠不完全吸收。吸收清除率（PeA/L）与部位有关，按结肠>十二指肠>空肠>回肠排列。这种顺序与 P-gp 肠内含量的顺序相反，提示可能受 P-gp 的影响。奥美拉唑共灌注增加了 PeA/L，从小肠和大肠段减少达卡他韦的 L95%也证明了这一点。胡椒碱的存在显著增强了达卡他韦通过空肠和回肠的吸收。达卡他韦在肠道中的吸收具有部位依赖性，表明其受 P-gp 外排的影响。这种作用被胡椒碱抑制。达卡他韦与奥美拉唑联合给药可增强肠道吸收，这一现象需要扩展到人体药代动力学研究中。
