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(英文)

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。

Oral bioavailability and intestinal disposition of dehydroandrographolide in rats

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(P app) 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.