Intestinal absorption features of Tripterygium wilfordii solid dispersion in rats with single-pass intestinal perfusion model
10.7501/j.issn.0253-2670.2019.02.028
- Author:
Jue WU
1
Author Information
1. 900 Hospital of the Joint Logistics Team
- Publication Type:Journal Article
- Keywords:
Celastrol;
Intestinal absorption kinetics;
Single-pass intestinal perfusion;
Solid dispersion;
Tripterygium wilfordii Hook. f.
- From:
Chinese Traditional and Herbal Drugs
2019;50(2):462-470
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the intestinal absorption kinetics of Tripterygium wilfordii (TW) solid dispersions and the effects of different intestinal segments, drug concentrations, pH value, and P-glycoprotein (P-gp) on intestinal absorption. Methods The absorption behavior was investigated in situ with a single-pass intestinal perfusion (SPIP) model in rats. The content of each index component was determined by HPLC. The gravimetric method was used to correct the data and calculate the absorption rate constant (Ka) and apparent permeability coefficient (Papp) of each index component. Results The index components of TW were absorbed in the whole intestine, and the absorption rate constant (Ka) of all the index components of TW solid dispersion was significantly increased than that of extract (P < 0.05), and had some differences among different segments. With the increase of drug concentration, the absorption of each index component had saturation phenomenon, which indicated that it may be carrier-mediated transport mechanism. Acidic environment (pH 5.4) was beneficial to the absorption of various index components, especially the acidic content celastrol. After adding P-gp inhibitor, the Ka and Papp of celastrol were significantly different from those without P-gp inhibitor (P < 0.05), which suggested that it may be the P-gp substrate. Conclusion All the index components of TW solid dispersion are absorbed in the whole intestine and have saturation phenomenon, which suggested the absorption may be carrier-mediated transport mechanism. Acidic environment is beneficial to the absorption of all components. The absorption process of celastrol is affected by drug concentration and P-gp inhibitor, which indicated that it may be P-gp substrate. The preparation of solid dispersing can significantly enhance the absorption of various components of TW, suggesting that all the index components are BCS II drugs, and the bioavailability of the preparation may be improved.
