摘要
The objective of this study was to investigate the absorption behavior of chikusetsusaponin IVa (CHS‐IVa) in the rat intestine using single‐pass intestinal perfusion (SPIP) and to classify CHS‐IVa into the biopharmaceutics classification system (BCS). The equilibrium solubility of CHS‐IVa was determined by the shaker method. The absorption mechanism of CHS‐IVa in the intestine was studied by comparing the Peff of different concentrations of CHS‐IVa. The intestinal site dependence of CHS‐IVa absorption was studied by comparing the Peff of the same concentration of CHS‐IVa in different intestinal segments. The relationship between CHS‐IVa and intestinal efflux protein was studied by perfusion with an efflux protein inhibitor. The permeability of CHS‐IVa was investigated by comparing the Peff of CHS‐IVa and the reported value. The solubility of CHS‐IVa over the pH range 1.0–7.5 was 14.4 ± 0.29 to 16.9 ± 0.34 mg/ml. The Peff of CHS‐IVa in the duodenum was 1.76 × 10−3 to 2.00 × 10−3 cm/min. The Peff of CHS‐IVa in the jejunum was 1.26 × 10−3 to 1.39 × 10−3 cm/min. The Peff of CHS‐IVa in the ileum was 1.25 × 10−3 to 1.31 × 10−3 cm/min. The Peff of CHS‐IVa in the colon was 1.02 × 10−3 to 1.08 × 10−3 cm/min. There was no statistical difference of the Peff in the four segments at different CHS‐IVa concentrations. The Peff of CHS‐IVa (0.07, 0.7 and 7.0 mg/ml) were all notably smaller than the reported Peff (3.00 × 10−3 cm/min) in the jejunum. The Peff of CHS‐IVa was not influenced by verapamil (P‐gp inhibitor), indomethacin (MRP inhibitor) and pantoprazole (BCRP inhibitor). CHS‐IVa was classified as high solubility, low permeability and BCS III. The main absorptive tracts were the upper intestinal tracts and the rank order of intestinal permeability was duodenum > jejunum ≈ ileum > colon. The transport mechanism of CHS‐IVa in all intestinal segments might be primarily passive transport. CHS‐IVa was not a substrate of P‐gp, MRP and BCRP.
摘要译文
本研究的目的是通过单次肠道灌注（SPIP）研究chikusetsusaponin IVa（CHS-IVa）在大鼠肠中的吸收行为，并将CHS-IVa分类为生物药物分类系统（BCS）。 CHS-IVa的平衡溶解度通过摇床法确定。通过比较不同浓度的CHS-IVa的P eff，研究了CHS-IVa在肠中的吸收机理。通过比较不同肠段中相同浓度的CHS-IVa的P eff来研究CHS-IVa吸收的肠部位依赖性。通过灌注外排蛋白抑制剂研究了CHS-IVa与肠道外排蛋白之间的关系。通过比较CHS-IVa的P eff和报道的值来研究CHS-IVa的渗透率。 CHS-IVa在1.0-7.5的pH范围内的溶解度为14.4±0.29至16.9±0.34 mg / ml。十二指肠中CHS-IVa的P eff为1.76×10 -3 至2.00×10 -3 cm / min。空肠中CHS-IVa的P eff为1.26×10 -3 至1.39×10 -3 cm / min。回肠中CHS-IVa的P eff为1.25×10 -3 至1.31×10 -3 cm / min。 CHS-IVa在结肠中的P eff为1.02×10 -3 至1.08×10 -3 cm / min。在不同CHS-IVa浓度下，四个区段的P eff均无统计学差异。 CHS-IVa的P eff（0.07、0.7和7.0 mg / ml）均显着小于空肠中报告的P eff（3.00×10 −3 cm / min）。 CHS-IVa的P eff不受维拉帕米（P-gp抑制剂），消炎痛（MRP抑制剂）和pan托拉唑（BCRP抑制剂）的影响。 CHS-IVa被分类为高溶解度，低渗透性和BCS III。主要吸收道是上消化道，肠道通透性的排列顺序是十二指肠>空肠≈回肠>结肠。 CHS-IVa在所有肠段的转运机制可能主要是被动转运。 CHS-IVa不是P-gp，MRP和BCRP的底物。
Wenzhou Zhang[1];Hui Liu[2];Chongfeng Liu[1]. Biopharmaceutics classification and intestinal absorption of chikusetsusaponin IVa[J]. Biopharmaceutics & Drug Disposition, 2019,40(8): 276-281