白藜芦醇衍生物大鼠在体肠吸收特性研究

Studies on absorptive characters of resveratrol derivative(E)-3,5,4'-trimethoxystilbene in rat intestine

目的:研究白藜芦醇衍生物[(E)-3,5,4′-三甲氧基-1,2-二苯乙烯(BTM-0512)]在大鼠肠道的吸收特性。方法:采用大鼠在体肠循环实验,考察不同的药物浓度、肠段及胆汁对吸收参数的影响。BTM-0512在大鼠肠循环液中的药物浓度采用HPLC法测定;循环液中酚红浓度采用UV法测定。结果:在肠道正常pH情况下,低、中、高3个浓度的BTM-0512的吸收速率常数(K_a)分别为0.6290,0.5329(扎胆管),0.5330(未扎胆管),0.6791 h^(-1),表明不同浓度BTM-0512在肠道的吸收速率常数相近,且胆汁对BTM-0512肠道吸收没有影响(P>0.05);在十二指肠、空肠、回肠,结肠的吸收速率常数分别为0.9492,0.5216,0.3835,0.1185 h^(-1),统计结果显示,不同肠段间吸收有明显差异(P<0.05)。结论:BTM-0512在肠道内是以被动扩散的方式被吸收,呈现一级动力学过程。因BTM-0512在整肠段均有吸收,剂型设计时可考虑肠溶制剂。

Objective：This paper is to study the absorptive characters of resveratrol derivative（E） -3,5,4＇ -trimethoxystilbene （BTM -0512） in rats＇ intestines.Methods：An in situ intestinal perfusion model was employed to investigate systemically the absorptive characters of resveratrol derivative BTM -0512 and the influence of different intestinal segments of rats,concentrations of the drug and bile to it.The concentration of BTM -0512 in intestine perfusate was measured by HPLC,and the concentration of phenolsulfonphthalein in intestine perfusate was measured by UV.Results：The absorptive rate constants（Ka） of BTM -0512 were 0.6290,0.5329 without ligation of bile ducts,0.5330 with ligation of bile ducts,0.6791 h^-1 at low,middle and high concentration and with or without ligation of bile ducts（P〉0.05）,the Ka of BTM -0512 were 0.9492,0.5216,0.3835,0.1185 h^-1 at duodenum, jejunum,ileum,colon respectively under the normal pH environment（P〈0.05）.Conclusion：The kinetic analyses showed that the intestinal absorption of BTM -0512 obeyed with passive transport mechanism and first order kinetics, BTM -0512 were absorbed at all the segment of intestine in rats.It was suggested that BTM -0512 could be designed as a enteric - coated formulation to benefit the bioavailability of it.