白藜芦醇衍生物大鼠在体肠吸收特性研究___

 

 

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(Ka)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^-1at 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.