白藜芦醇衍生物(BTM-0512)在大鼠体肠吸收特性研究

Studies on Absorptive Characters of Resveratrol Derivative(E)-3,5,4′-trimethoxystilbene(BTM-0512) in Rat's Intestines

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值情况下,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)、0.6791h^(-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-05 12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 (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 on 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(K) of BTM-0512 were 0.6290,0.5329(without ligation of bile ducts),0.5330(with ligation of bile ducts),0.6791h^(-1)at low,middle and high concentration with or without ligation of bile ducts(P> 0.05),the K_a 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.