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Biopharmaceutics classification and intestinal absorption of chikusetsusaponin IVa
Author(s) -
Zhang Wenzhou,
Liu Hui,
Liu Chongfeng
Publication year - 2019
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2200
Subject(s) - biopharmaceutics classification system , jejunum , chemistry , ileum , absorption (acoustics) , passive transport , intestinal permeability , solubility , medicine , biochemistry , materials science , organic chemistry , composite material , membrane
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 P eff of different concentrations of CHS‐IVa. The intestinal site dependence of CHS‐IVa absorption was studied by comparing the P eff 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 P eff 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 P eff of CHS‐IVa in the duodenum was 1.76 × 10 −3 to 2.00 × 10 −3 cm/min. The P eff of CHS‐IVa in the jejunum was 1.26 × 10 −3 to 1.39 × 10 −3 cm/min. The P eff of CHS‐IVa in the ileum was 1.25 × 10 −3 to 1.31 × 10 −3 cm/min. The P eff 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 P eff in the four segments at different CHS‐IVa concentrations. The P eff of CHS‐IVa (0.07, 0.7 and 7.0 mg/ml) were all notably smaller than the reported P eff (3.00 × 10 −3 cm/min) in the jejunum. The P eff 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.