拉马宁碱的大鼠在体肠吸收机制研究

目的 研究拉马宁碱大鼠在体肠吸收机制.方法 采用大鼠在体单向肠灌流吸收实验模型,应用重量法校正灌流液体积,通过反相高效液相色谱法测定灌流液中药物浓度,并考察吸收部位、药物质量浓度、P-糖蛋白(P-gp)抑制剂及有机阳离子转运蛋白(OCTs)抑制剂对药物吸收的影响.结果 拉马宁碱在整肠段均有吸收,吸收速率常数(Ka)和表观吸收系数(Papp)分别按照回肠、结肠、空肠、十二指肠的顺序下降；2-20μg/mL的药物质量浓度对Ka和Papp无显著影响(P＞0.05)；含P-gp抑制剂组与不含P-gp抑制剂组相比,Ka和Papp无显著性差异(P＞0.05)；含OCTs抑制剂组与不含OCTs抑制剂组相比,Ka和Papp.也无显著性差异(P＞0.05).结论 拉马宁碱为全肠段吸收,吸收机制为被动扩散,且P-gP及OCTs对药物的小肠吸收基本无影响.

Intestinal absorption of lehmannine in rat

AIM To investigate the rat’s intestinal absorption of lehmannine extracted from Sophora alopecuroides L.METHODS Single-pass perfusion was applied and the gravimetry was used to correct the perfusion volume.The concentrations of lehmannine in intestinal fluid was measured by HPLC.Absorption site,drug concentration,inhibiting effect of P-glycoprotein(P-gp) and organic cation transporters(OCTs) were studied.RESULTS Lehmannine was absorbed in the whole intestine.Its absorption constant(Ka) and apparent absorption coefficient(Papp) were as follows: ileum>colon>jejunum>duodenum.Drug concentration had little connection with Ka and Papp(P>0.05).There was no significant difference in Ka and Papp between presence of P-gp/OCTs inhibitor and no P-gp /OCTs inhibitor(P>0.05).CONCLUSION Lehmannine is absorbed in the whole intestine,belonging to a passive diffusion process,and does not relate to lehmannine concentrations,P-gp and OCTs.