Influence of Shenxiong Glucose Injection on the Activities of Six CYP Isozymes and Metabolism of Warfarin in Rats Assessed Using Probe Cocktail and Pharmacokinetic Approaches

Molecules

Zipeng Gong¹  Yonglin Wang¹  Chunhua Liu¹  Yuan Lu¹  Ting Liu¹  Jiang Zheng¹  Yueting Li¹  Lin Zheng¹  Jie Pan¹  Jia Sun¹  Jing Huang²  Yongjun Li² 

[1] Key Laboratory of Pharmaceutics of Guizhou Provincial, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China;School of Pharmacy, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China;

关键词: CYP isozyme;    herb-drug interaction;    Shenxiong glucose injection;    warfarin;   

DOI  :  10.3390/molecules22111994

来源: DOAJ

【 摘 要 】

Shenxiong glucose injection (SGI), a traditional Chinese medicine (TCM) preparation, has been widely used for the treatment of various cardiovascular and cerebrovascular diseases for many years. We assessed the potential influences of SGI on the activities of six CYP enzymes (CYP1A2, CYP2C11, CYP2C19, CYP2D4, CYP2E1, and CYP3A2) and on the pharmacokinetics of warfarin in rats. We compared plasma pharmacokinetics of six probe drugs (caffeine/CYP1A2, tolbutamide/CYP2C11, omeprazole/CYP2C19, metoprolol/CYP2D4, chlorzoxazone/CYP2E1, and midazolam/CYP3A2) and of warfarin between control and SGI-pretreated groups, to estimate the effect on the relative activities of the six isozymes and warfarin metabolism. There were no significant differences in the pharmacokinetic parameters of caffeine, omeprazole, metoprolol, chlorzoxazone, and midazolam between the SGI-pretreated and control groups. However, many pharmacokinetic parameters of tolbutamide in SGI-pretreated rats were affected significantly (p < 0.05), and indicated tolbutamide metabolism in the former group was markedly slower. Moreover, SGI reduced the clearance of warfarin. These results suggested SGI showed no effects on the enzyme activities of rat CYP1A2, CYP2C19, CYP2D4, CYP2E1, and CYP3A2, but inhibited the enzyme activity of CYP2C11, and improved the blood concentration of warfarin. This suggests that the dose of warfarin may need be adjusted when co-administrated with SGI.

【 授权许可】

Unknown