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

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.