南方医科大学学报

南方医科大学学报 ›› 2012, Vol. 32 ›› Issue (08): 1074-.

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Oral bioavailability and intestinal disposition of dehydroandrographolide in rats

叶玲，梁福贵，杨晓珊，石剑，王峰，刘薇，赵洁，刘中秋   

  • 出版日期:2012-08-20 发布日期:2012-08-20

YE Ling, LIANG Fugui, YANG Xiaoshan, SHI Jian,WANG Feng, LIUWei, ZHAO Jie, LIU Zhongqiu   

  • Online:2012-08-20 Published:2012-08-20

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摘要： 目的研究脱水穿心莲内酯在大鼠体内的口服生物利用度和肠道处置，为其在临床的使用和开发提供有用的信息。方法
研究脱水穿心莲内酯在大鼠体内的药代动力学行为。采用Caco-2细胞模型和大鼠在体肠灌流模型研究脱水穿心莲内酯在大鼠
体内的肠道处置。结果脱水穿心莲内酯的口服绝对生物利用度是11.92%。在Caco-2细胞模型中，脱水穿心莲内酯从基底膜到
顶端膜方向转运的表观渗透系数（5.37×10-5 cm/s）约等于其从相反方向转运的表观渗透系数（4.56×10-5 cm/s），表明外排转运蛋
白没有参与脱水穿心莲内酯的细胞转运。大鼠在体肠灌流模型中，脱水穿心莲内酯在不同肠段的吸收没有显著性差异，同时没
有代谢。脱水穿心莲内酯经胆汁排泄，其排泄量约占吸收量的0.1%。在P-糖蛋白和乳腺癌蛋白抑制剂的作用下，脱水穿心莲内
酯在不同肠段的吸收和胆汁排泄量都没有提高(P>0.05) 。结论脱水穿心莲内酯的口服生物利用度是11.92%。它在肠道中的
吸收较好，不进行代谢。外排转运蛋白例如P-糖蛋白和乳腺癌蛋白不参与脱水穿心莲内酯的细胞转运。

Abstract: Objective Dehydroandrographolide (DP) from Andrographis paniculata (Burm. F.) Nees is a potential anticancer
agent. This study aimed to investigate the oral bioavailability and intestinal disposition of DP to provide useful information for
the development of DP as a new candidate anticancer drug. Methods The pharmacokinetics of DP was evaluated in rats, and
its intestinal disposition was determined using cultured Caco-2 cells and a single-pass rat intestinal perfusion model. Results
The oral bioavailability of DP was 11.92% in rats. The apparent permeability coefficient (Papp) of DP from the basolateral side
(B) to the apical side (A) (5.37×10-5 cm/s) of the Caco-2 model was roughly equal to that from A to B (4.56×10-5 cm/s), suggesting
no involvement of the efflux transporter(s). In the perfusion model, no significant difference was found in the effective
permeability (P*eff) of DP between the 4 segments of the intestine. No significant metabolism of DP was detected in the
intestinal perfusates. The amount of DP found in the bile was only about 0.1% of the absorbed amount. The P*eff and bile
amounts of DP were not significantly increased by P-glycoprotein (P-gp) inhibitor or breast caner resistant protein (BCRP)
inhibitor (P>0.05). Conclusion The bioavailability of DP was 11.92% in rats. DP has good absorption and metabolism stability
in the intestine. The efflux transporters such as P-gp and BCRP do not participate in DP transport.