巴戟甲素的大鼠在体肠吸收动力学

目的:考察巴戟甲素大鼠在体肠吸收的动力学特征。方法:采用大鼠在体单向灌流法,利用HPLC-ELSD测定巴戟甲素的含量,研究巴戟甲素在小肠段(十二指肠、空肠、回肠)和结肠的吸收情况,并考察药物质量浓度(43.92,87.84,175.68 mg·L-1),灌流液p H(5.4,6.8,7.4)和P糖蛋白(P-gp)抑制剂(0,0.2,0.5 mmol·L-1)对巴戟甲素吸收的影响。结果:巴戟甲素为全肠道吸收的药物,吸收速率与灌流液p H和肠段部位有关,其吸收速率按十二指肠、空肠、回肠和结肠的顺序依次下降。在实验浓度范围内,十二指肠、空肠、回肠和结肠的吸收速率常数分别在2.752~2.861,1.435~1.574,1.353~1.403,1.144~1.301 h-1。与原药组相比,含高浓度P-gp抑制剂药物组Papp显著增加(P<0.05)。结论:巴戟甲素在十二指肠、空肠、回肠和结肠的吸收以被动扩散方式为主,其吸收动力学符合一级过程。

In situ Intestinal Absorption Kinetics of Bajijiasu in Rats

Objective: To study the in situ intestinal absorption kinetics of bajijiasu in rats. Method: The absorption of bajijiasu in the small intestine (duodenum, jejunum and ileum) and colon of rats was investigated using an in situ single-pass perfusion method. The drug concentration was measured by HPLC-ELSD. The effects on intestinal absorption of different drug concentration (43.92, 87.84, 175.68 mg · L^-1), different pH in perfusate (5.4, 6.8, 7.4) and P-glycoprotein (P-gp)inhibitor (0, 0.2, 0.5 mmol · L^-1) were conducted. Result: Bajijiasu could be absorbed in the whole intestine, and its absorption rate was influenced by the pH of the perfusion solution and intestinal segments. The absorption rate in duodenum, jejunum, ileum and colon was 2.752-2.861, 1.435-1.574, 1.353-1.403, 1.144-1.301 h^-1, respecvticvely, the rate declined in turn. P_app in the group containing the P-gp inhibitor increased markedly. Conclusion: The absorption of bajijiasu shows passive diffusion in the general intestinal segments with the first-order kinetic process.