| Caco-2 cell monolayer as a vitro model is well correlate with intestine-like in researching absorption of compound. So, the model is used to investigate absorption rate and the relation between structure of drug molecule and obsorption.In this paper, absorption and metabolism of aconitine, mesaconitine, and hypaconitine were studied by using Caco-2 cell monolayers as an intestinal epithelial cell model. Initial concentrations of them were 50μmol/L, 75μmol/L and 100μmol/L respectively. The apparent permeability (Papp) of each compound was obtained in both apical side to basolateral side and basolateral side to apical side. When their concentrations were 50μmol/L, the Papp values of the three compounds from apical side to basolateral side were 30.56±4.82×10-6cm﹒s-1, 25.00±2.87×10-6cm﹒s-1 and 25.52±4.60×10-6cm﹒s-1 respectively. The Papp values of them for 75μmol/L were 32.90±5.49×10-6cm﹒s-1, 27.73±4.01×10-6cm﹒s-1 and 24.37±2.54×10-6cm﹒s-1 respectively. The Papp values of them for 100μmol/L were 29.25±4.14×10-6cm﹒s-1, 24.29±3.75×10-6cm﹒s-1 and 25.88±1.74×10-6cm﹒s-1 respectively. Under identical condition, when their concentration were 50μmol/L, the Papp values of the three compounds from basolateral side to apical side were 21.35±2.58, 22.50±4.11×10-6cm﹒s-1 and 20.49±2.34×10-6cm﹒s-1 respectively. The Papp values of them for 75μmol/L were 21.91±3.59×10-6cm﹒s-1, 23.10±3.75×10-6cm﹒s-1 and 22.62±3.81×10-6cm﹒s-1 respectively. The Papp values of them for 100μmol/L were 24.59±3.74×10-6cm﹒s-1, 19.23±2.91±3.75×10-6cm﹒s-1 and24.06±2.65×10-6cm﹒s-1 respectively. These observations suggest the three compounds can be all facile absorbed through Caco-2 cell monolayers. As a result, we can deduce that the transportations of the three compounds are passive.By using Caco-2 cell monolayers as an intestinal epithelial cell model, transportations of the three compounds were studied when two compounds were mixed (aconitine and mesaconitine; aconitine and hypaconitine; mesaconitine and hypaconitine). Initial concentrations of them were 50μmol/L, 75μmol/L and 100μmol/L respectively. We got the result as following. For three concentrations of aconitine in the mixture of aconitine and mesaconitine, the Papp values were 26.00±0.25×10-6cm﹒s-1, 30.68±0.31×10-6cm﹒s-1 and 33.74±0.28×10-6cm﹒s-1 from apical side to basolateral side, and 21.88±0.29×10-6cm﹒s-1, 22.62±0.20×10-6cm﹒s-1 and 20.70±0.28×10-6cm﹒s-1 from basolateral side to apical side, respectively, and the Papp values of mesaconitine in the mixture were 40.22±0.29×10-6cm﹒s-1, 25.42±0.31×10-6cm﹒s-1 and 30.66±0.34×10-6cm﹒s-1 from apical side to basolateral side, and 27.68±0.19×10-6cm﹒s-1, 19.56±0.28×10-6cm﹒s-1 and 27.20±0.21×10-6cm﹒s-1 from basolateral side to apical side, respectively; For three concentrations of aconitine in the mixture of aconitine and hypaconitine, the Papp values were 35.96±0.29×10-6cm﹒s-1, 36.58±0.19×10-6cm﹒s-1 and 34.92±0.22×10-6cm﹒s-1 from apical side to basolateral side, and 22.66±0.33×10-6cm﹒s-1, 22.90±0.31×10-6cm﹒s-1 and 18.12±0.28×10-6cm﹒s-1 from basolateral side to apical side, respectively, and the Papp values of hypaconitine in the mixture were 24.96±0.20×10-6cm﹒s-1, 27.21±0.19×10-6 cm﹒s-1 and 31.82±0.20×10-6cm﹒s-1 from apical side to basolateral side, and 26.94±0.15×10-6cm﹒s-1, 28.60±0.29×10-6cm﹒s-1 and 23.26±0.16×10-6cm﹒s-1 from basolateral side to apical side, respectively; For three concentrations of mesaconitine in the mixture of mesaconitine and hypaconitine, the Papp values were 32.44±0.26×10-6cm﹒s-1,35.36±0.27×10-6cm﹒s-1 and 32.40±0.17×10-6cm﹒s-1 from apical side to basolateral side, and 24.96±0.23×10-6cm﹒s-1, 21.96±0.22×10-6cm﹒s-1 and 23.52±0.22×10-6cm﹒s-1 from basolateral side to apical side, respectively, and the Papp values of hypaconitine in the mixture were 31.54±0.19×10-6cm﹒s-1, 32.96±0.30×10-6cm﹒s-1 and 31.08±0.21×10-6cm﹒s-1 from apical side to basolateral side, and 24.16±0.11×10-6cm﹒s-1, 24.20±0.26×10-6cm﹒s-1 and 24.58±0.25×10-6cm﹒s-1 from basolateral side to apical side, respectively. These observations suggest the absorption of anyone in mixture was higher than that of single respective compound. These maybe due to the synergy of those compounds when any two of them mixed together. The interaction between mesaconitine and hypaconitine is the strongest. |
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