Drug-Drug Interaction (DDI) between Felodipine and Irinotecan During the Treatment of Ovarian Cancer

作者：Chen, Fang; Zhou, Ping^*

来源：Latin American Journal of Pharmacy, 2018, 37(3): 449-451.

• carboxylesterase (CES) 2
• drug-drug interaction (DDI)
• irinotecan
• ovarian cancer
• SN-38

Ovarian cancer remains to threaten the health of humans, and irinotecan is being developed to treat ovarian cancer. This study aims to investigate the inhibition of felodipine (a long-acting 1,4-dihydropyridine calcium channel blocker (CCB)b) on the activity of carboxylesterase (CES) 2, which is the key enzyme catalyzing the hydrolysis of irinotecan to form its active metabolite SN-38. In vitro human liver microsomes (HLMs)-catalyzed hydrolysis of fluorescein diacetate (FD) was used to determine the inhibition of felodipine on the activity of CES2. Felodipine 100 mu M was used as the initial screening concentration, and the residual activity (RA) was calculated using the following equation: Residual activity (RA) = the activity of CES2 at 100 mu M of felodipine/the activity of CES2 at 0 uM of felodipine x 100%. Felodipine inhibited more than 90% activity of CES2. In conclusion, this study demonstrated the inhibition of felodipine on the activity of CES2, demonstrating the potential drug-drug interaction (DDI) between felodipine and irinotecan. Additionally, DDI also existed between felodipine and clinical drugs mainly undergoing CES2-catalyzed hydrolysis metabolism.

• 出版日期2018
• 单位新疆医科大学