Investigation on the intestinal absorption characters of harmine derivative H-2-168 using Caco-2 cells and single-pass intestinal perfusion
XU Qin-wei
TENG Liang
CHEN Bei
MA Qin
LI Jin-xin
HUANG Yu-jie
GAO Hui-jing
Abstract：Objective:To investigate the intestinal absorption characteristics of harmine derivative H-2-168 using Caco-2 cells model and in situ single-pass intestinal perfusion method.Methods:The Caco-2 cell monolayer model and in situ single pass intestinal perfusion model of rat were established.The concentrations of H-2-168 in cell permeation fluid and intestinal perfusion fluid were determined by HPLC.The changes of apparent permeability coefficient(Papp)of H-2-168 in Caco-2 cell model and those of absorption rate constant(Ka)and Papp in in situ single pass intestinal perfusion model of rat under different influence factors(intestinal segment,concentration,pH and P-glycoprotein inhibitor)were investigated.Results:In Caco-2 cell model,Papp values at medium and high concentrations of H-2-168 were significantly higher than that at low concentration(P<0.05),but Papp at high concentration was slightly lower than that at medium concentration,showing a high concentration saturation phenomenon.H-2-168 was absorbed in the whole intestine of rats,with Ka and Papp decreased significantly with the increase of drug concentration(P<0.05).Ka and Papp at pH 7.4 were significantly higher than those at pH 5.4.There were no significant changes in the absorption parameters before and after the addition of P-glycoprotein inhibitor(P>0.05).Conclusion:H-2-168 is a well-absorbed drug,and its absorption mechanism may involve active transport or facilitated diffusion,and it is not a substrate of P-glycoprotein.
Keywords：harmine derivativeCaco-2 cell modelin situ single-pass intestinal perfusionintestinal absorption
Publication Date：2025-09-15
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：7( 1845-1851 )