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Taking major components of conjugated estrogen (CE), sodium equilin sulfate (EqS) and sodium estrone sulfate (ES), as examples to investigate their absorption characteristics in the rat intestine, and to evaluate two intestinal models.
Determination method of EqS and ES using atenolol as an internal standard by HPLC was delevloped. Models of in situ single-pass intestinal perfusions (SPIP) and Ussing Chamber rat intestine were applied for this study. The samples of intestinal sac fluid and receiving fluid at different time points after dosages of EqS+ES and atenolol. The parameters of effective permeability (Peff) and apparent permeability (Papp) were calculated and compared with that of atenolol.
The linearity of the HPLC analysis methods for the two intestinal models is well correlated within a certain concentration range (r>0.999), the intra-day and inter-day precisions are both below 15%, the accuracy is between 85%~115%, and the recovery is greater than 70%. In SPIP rat model, no statistical difference was found between the Peff of EqS+ES (jejunum: 0.22±0.07×10-4, cm·s-1; ileum: 0.24±0.08×10-4, cm·s-1) and atenolol (jejunum: 0.18±0.11×10-4, cm·s-1; ileum: 0.32±0.15×10-4, cm·s-1) in jejunum and ileum (P空=0.373; P回=0.128). In Ussing Chamber rat intestine model, EqS+ES and atenolol were absorbed in all intestinal segments of rats (duodenum: 1.83±0.77×10-6, cm·s-1, 5.46±0.80×10-6, cm·s-1; jejunum: 6.93±1.43×10-6, cm·s-1, 10.04±1.16×10-6, cm·s-1; ileum: 6.96±1.28×10-6, cm·s-1, 6.28±0.82×10-6; colon: 10.03±2.07×10-6, cm·s-1, 11.09±1.08×10-6, cm·s-1). There was no statistical difference between Papp of EqS+ES and atenolol in the ileum and colon (Pileum=0.251; Pcolon=0.263). Atenolol is a alkaline compound, the permeability of which in ileum was higher than that in Jejunum theoretically. The in vitro model differs from the theory.
CE can be considered as a drug with moderate permeability. SPIP rat model among the two models seems more accurate and reliable.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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