小檗碱对黄芩苷在大鼠中药代动力学的影响

Effect of Berberine on Pharmacokinetics of Baicalin in Rats

目的:研究小檗碱影响黄芩苷药代动力学行为的机制。方法:三组大鼠分别ig黄芩苷、黄芩苷与小檗碱的混合物以及先小檗碱、2h后再黄芩苷。用HPLC法测定血浆中的黄芩苷浓度并计算其药代动力学参数。采用肠外翻实验研究测定黄芩苷在十二指肠、空肠、回肠段的吸收情况。测定黄芩苷在给小檗碱处理大鼠和正常大鼠粪便中的分解曲线。结果:体内实验中,同时给药组中黄芩苷的血药浓度和AUC与单用组相比显著降低,分开给药组情况有所改善。体外实验中,黄芩苷在肠中吸收存在区域性:回肠>十二指肠>空肠。黄芩苷在ig小檗碱后的粪便混悬液中的降解要比在ig小檗碱前的粪便混悬液中的降解慢。结论:小檗碱显著降低口服黄芩苷的AUC,小檗碱可能通过与黄芩苷生成共沉淀和抑制β-葡萄糖醛酸酶活性进而减少黄芩苷转化成黄芩素影响黄芩苷的吸收。

AIM： To investigate the mechanism of effects of beberine to pharmacokinetics of baicalin in rats. METHODS： Three groups of rats received oral- administration of baicalin alone, co-administration of baicalin and berberine and separate administration of berberine and baicalin, respectively. Blood samples were obtained in a designed time. Concentrations of baicalin in plasma were measured by HPLC and the corresponding pharmacokinetic parameters were estimated. The everted sac experiment was introduced to investigate the absorption mechanism of baicalin and fermentation of baicalin in feces suspension experiment was introduced to investigate whether berberine affected the degradation of baicalin. RESULTS： In vivo, the blood concentration and exposure of baicalin significantly decreased after oral co-administration of baicalin （200 mg·kg^-1） and berberine （240 mg·kg^-l） in rats as compared with single administration of baicalin （ 200 mg· kg^- 1 ）. The situation was improved in separate administration of baicalin （200 mg· kg^- 1 ） and berberine （240 mg·kg^-1）. In vitro, the transport of baicalin showed a regional variation in rat intestine and the transport rate of baicalin was ileum 〉 duodenum 〉 jejunum. Baicalin was degraded when incubated in feces suspensions of rats. The degradation of baicalin in feces suspensions of rats previously treated with berberine （240 mg· kg^- l ） was slower than that in the control. CONCLUSION： The experimental findings indicated that the co-precipitation between baicalin and berberine might decrease the exposure of baicalin, also berberine could decrease the systematic exposure of baicalin via inhibiting the hydrolization of baicalin. These interactions should be paid attention to in clinical studies when baicalin is administered in combination with berberine.