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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(5.37×10-5cm/s)约等于其从相反方向转运的表观渗透系数(4.56×10-5cm/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。
Objective To study the oral bioavailability and intestinal management of dehydroandrographolide in rats and provide useful information for its clinical use and development. Methods The pharmacokinetics of dehydroandrographolide in rats were studied. The intestinal transit of andrographolide in rats was studied by Caco-2 cell model and rat intestinal perfusion model. Results The oral absolute bioavailability of dehydroandrographolide was 11.92%. In the Caco-2 cell model, the apparent permeation coefficient (5.37 × 10 -5 cm / s) of dehydrated andrographolide transport from the basal membrane to the apical membrane is approximately equal to its apparent permeability coefficient (4.56 × 10 -5 cm / s), indicating that efflux transporter did not participate in the cellular transport of dehydroandrographolide. Rats in the intestinal perfusion model, dehydration andrographolide in different intestinal absorption was no significant difference, while no metabolism. Dehydration andrographolide bile excretion, the amount of its absorption accounts for about 0.1% of absorption. Under the action of P-glycoprotein and breast cancer protein inhibitor, the absorption of dehydrated andrographolide in different intestinal segments and the amount of bile excretion did not increase (P> 0.05). Conclusion The oral bioavailability of dehydroandrographolide is 11.92%. It absorbs well in the gut without metabolism. Luteae transporters such as P-glycoprotein and breast cancer proteins do not participate in the cellular transport of dehydroandrographolide.