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《The Chinese Journal of Clinical Pharmacology》 2017-16
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Effect of Radix astragali injection on the cytochrome P450 activities with ultrahigh performance-LC-MS/MS in rats

YUAN Hong-chang;ZHOU Yong-hao;LIU Rong;ZHENG Xiao-kang;CHEN Ke-li;ZENG Nan;School of Pharmacy, Chengdu University of Traditional Chinese Medicine;Henan Vocational College of Tuina;Medical College of Henan University of Science and Technology;  
Objective To study the effect of Radix astragali injection( RA) on the activities of cytochrome P450 2D6( CYP2D6),2C19,3A4,1A2 and 2C9 by ultrahigh performance-LC and tandem mass spectrometry( UHPLC-MS/MS). Methods The activities of CYP2D6,2C19,3A4,1A2 and 2C9 were evaluated based on pharmacokinetics of metoprolol,omeprazole,midazolam,phenacetin and tolbutamide( five probe drugs) respectively. SD rats were assigned to two groups: control group and experimental group and the rats in the two groups were given 0. 9%Na Cl and RA 10 mL·kg~(-1)by intraperitoneal injection for consecutive 7 days respectively. On the 7th day,after intraperitoneal injection for 30 min,a mix dose of five probe drugs was intragastric administration to all rats. Blood samples were collected at different times for UHPLC-MS/MS analysis. Pharmacokinetic parameters of five probe drugs were assessed between the two groups respectively. Results For metoprolol,omeprazole,phenacetin and tolbutamide, the AUC_(0-t) in RA group decreased by 37. 8%, 55. 5%, 40. 9% and 38. 9% respectively, the C_(max) in experimental group decreased by 25. 4%,33. 6%,14. 6% and 40. 2% respectively. While the AUC_(0-t) and C_(max) of midazolam in experimentalgroup increased significantly by 60. 1% and 195% respectively. RA could increase the total amount of midazolam absorbed into blood,while decreasing the total amounts of metoprolol,omeprazole,phenacetin and tolbutamide absorbed compared with control group respectively. The method of validation conformed to the requirements of the relevant rat pharmacokinetic guidelines. Conclusion This method was successfully employed to assess the effect of RA on the activities of CYP2D6,2C19,3A4,1A2 and 2C9 in vivo. RA could inhibit the activity of CYP3A4,while inducing the activities of CYP2D6,2C19,1A2 and 2C9.
【Key Words】: Radix astragali injection ultrahigh-performance LC-MS/MS cytochrome P450 pharmacokinetics
【Fund】: 四川省青年科技创新研究团队基金资助项目(2014TD0007)
【CateGory Index】: R285.5
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