Metabolic and pharmacokinetic studies of scutellarin in rat plasma, urine, and feces  

作　　者：Jian-feng XING Hai-sheng YOU Ya-lin DONG Jun LU Si-ying CHEN Hui-fang ZHU Qian DONG Mao-yi WANG Wei-hua DONG 

机构地区：[1]Department of Pharmacy, Medical College, Xi-an Jiaotong University, Xi-an 710061, China [2]Department of Pharmacy, the First Affiliated Hospital, Medical College, Xi-an Jiaotong University, Xi-an 710061, China

出　　处：《Acta Pharmacologica Sinica》2011年第5期655-663,共9页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by the National Natural Science Foundation of China （No 30973673 and 30973578）.

摘　　要：Aim： To study the metabolic and pharmacokinetic profile of scutellarin, an active component from the medical plant Erigeron breviscapus （Vant） Hand-Mazz, and to investigate the mechanisms underlying the low bioavailability of scutellarin though oral or intravenous administration in rats. Methods： HPLC method was developed for simultaneous detection of scutellarin and scutellarein （the aglycone of scutellarin） in rat plasma, urine and feces. The in vitro metabolic stability study was carried out in rat liver microsomes from different genders. Results： After a single oral dose of scutellarin （400 mg/kg）, the plasma concentrations of scutellarin and scutellarein in female rats were significantly higher than in male ones. Between the female and male rats, significant differences in AUC, tmax2 and Cmax2 for scutel- larin were found. The pharmacokinetic parameters of scutellarin in the urine also showed significant gender differences. After a single oral dose of scutellarin （400 mg/kg）, the total percentage excretion of scutellarein in male and female rats was 16.5% and 8.61%, respectively. The total percentage excretion of scutellarin and scutellarein in the feces was higher with oral administration than with intravenous administration. The in vitro t1/2 and GLint value for scutellarin in male rats was significantly higher than that in female rats. Conclusion： The results suggest that a large amount of ingested scutellarin was metabolized into scutellarein in the gastrointestinal tract and then excreted with the feces, leading to the extremely low oral bioavailability of scutellarin. The gender differences of pharma- cokinetic parameters of scutellarin and scutellarein are due to the higher GLint and lower absorption in male rats.Aim： To study the metabolic and pharmacokinetic profile of scutellarin, an active component from the medical plant Erigeron breviscapus （Vant） Hand-Mazz, and to investigate the mechanisms underlying the low bioavailability of scutellarin though oral or intravenous administration in rats. Methods： HPLC method was developed for simultaneous detection of scutellarin and scutellarein （the aglycone of scutellarin） in rat plasma, urine and feces. The in vitro metabolic stability study was carried out in rat liver microsomes from different genders. Results： After a single oral dose of scutellarin （400 mg/kg）, the plasma concentrations of scutellarin and scutellarein in female rats were significantly higher than in male ones. Between the female and male rats, significant differences in AUC, tmax2 and Cmax2 for scutel- larin were found. The pharmacokinetic parameters of scutellarin in the urine also showed significant gender differences. After a single oral dose of scutellarin （400 mg/kg）, the total percentage excretion of scutellarein in male and female rats was 16.5% and 8.61%, respectively. The total percentage excretion of scutellarin and scutellarein in the feces was higher with oral administration than with intravenous administration. The in vitro t1/2 and GLint value for scutellarin in male rats was significantly higher than that in female rats. Conclusion： The results suggest that a large amount of ingested scutellarin was metabolized into scutellarein in the gastrointestinal tract and then excreted with the feces, leading to the extremely low oral bioavailability of scutellarin. The gender differences of pharma- cokinetic parameters of scutellarin and scutellarein are due to the higher GLint and lower absorption in male rats.

关 键 词：SCUTELLARIN SCUTELLAREIN metabolism PHARMACOKINETICS excretions gender differences 

分 类 号：S859.796[农业科学—临床兽医学] TQ460.6[农业科学—兽医学]