Rat intestinal absorption trait of danshensu and protocatechuic aldehyde in Salviae Miltiorrhizae Radix et Rhizoma extract by single pass perfusion / 中草药

ABSTRACT

Objective: To investigate the rat intestinal absorption kinetics of danshensu (DS) and protocatechuic aldehyde (PA) in Salviae Miltiorrhizae Radix et Rhizoma extract. Methods: In situ single pass intestinal perfusion model was employed to investigate the effects of perfusion rate, perfusion solution pH value, bile duct ligation, drug concentrations, absorption sites and P-glycoprotein (P-gp) on absorption of DS and PA, and perfusion volume was corrected by gravimetric method. Meanwhile, the concentration of DS and PA in the perfusate were determined by HPLC. Results: The drug absorption constant (Ka) and apparent absorption coefficient (Papp) of DS and PA increased linearly along with the increasing perfusion rates among the ranges of 0.2-0.8 mL/min. pH value of perfusion solution affected drug absorption (P < 0.05), Ka and Papp of DS and PA decreased with increasing pH value at pH values of 7.4, 6.8, and 5.5. And at pH value of 5.5 and 6.8, the absorption had no significant difference, but there was significant difference at pH value between 5.5 and 7.4 (P < 0.05). There was no significant difference in Ka and Papp value between bile duct ligation group and no ligation group. At different absorption sites, K a and Papp of DS in the duodenum, jejunum, ileum, and colon sequence have a downward trend, but not for PA, while PA could be absorbed well at all intestinal segments. In the drug concentrations of 0.8, 1.5, and 2.2 mg/mL, Ka, and Papp of DS decréased with higher concentrations, and PA absorption parameter has non-obvious changes. There was no significant difference in Ka and Papp between the presence of P-gp inhibitor and no P-gp inhibitor. Conclusion: Perfusion rate and pH value have significant influence on absorption of DS and PA. Two water-soluble ingredients could be absorbed at all intestinal segments and DS has better absorption at former intestinal segments. The concentration of the extract has no influence on its absorption parameters of PA, which preliminarily demonstrates that PA is absorbed by passive diffusion mechanism. However, absorption of DS is affected by concentration, indicating that in addition to passive diffusion, it may also have active absorption or facilitation diffusion in absorption process of DS. Moreover, two ingredients are not affected by P-gp efflux.