Biopharmaceutics classification and intestinal absorption of chikusetsusaponin IVa.

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.