Intestinal absorption of forsythoside A by rat circulation in situ

This study is to investigate the effects of concentration, intestinal section, pH, paracellular route, substrate/inhibitor of enzyme (CYP3A) and proteins (P-gp, MRP2, SGLT1) on the absorption of forsythoside A.  The absorption of three concentrations (2.6, 5.2, and 10.4 μg·mL⁻¹) of forsythoside A in different intestinal  segments was studied with phenol red as the marker by rat circulation in situ.  The results showed that the  residue of forsythoside A with different concentrations had little significant difference from that obtained after perfusing via duodenum, jejunum, ileum and colon, which indicated that the absorption of forsythoside A was passive diffusion and had no difference in different segments of rat intestine.  The residue of forsythoside A  increased to 466.160 and 463.429 μg respectively when cyclosporine (4 μg·mL⁻¹) or midazolam (50 μmol·L⁻¹) was added to the circulation fluid, which showed significant difference compared to the control group (P < 0.05).  Moreover, the residue of forsythoside A showed a tendency of increase with the increase of cyclosporine or  midazolam.  When digoxin (50 μmol·L⁻¹) or EDTA (10 μg·mL⁻¹) was added to the circulation fluid, the residue of forsythoside A decreased to 325.110 and 369.888 μg respectively, which showed significant differenceas compared to the control group (P < 0.05).  Besides, the residue of forsythoside A showed a tendency of reduction with the increase of digoxin or EDTA.  However, there is no significant change in the absorption of forsythoside A when the different concentrations of mannitol were added to the circulation fluid.  The results above indicated that the absorption of forsythoside A was mainly passive diffusion and involved paracellular route at the same time.  In addition, the substrates of P-gp or CYP3A had dose-dependent effect on the absorption of forsythoside A.