In Vitro To Estimate Bifendate Cause DDI Possibilities

Objective: To examine the inhibitory effects of Bifendate towards seven major cytochrome P450 (CYP) isoforms and to evaluate it's potential of drug-drug interactions.Methods: The inhibitory effects of bifendate (1, 5, 10, 25, 50, 100μM) against the activities of seven CYP isoforms including CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 were examined in human liver microsomes. Meanwhile, Bifendate was tested for their mechanism-based inhibition on seven major CYPs. Bifendate was preinc- ubated with microsomes and a NADPH-generating system for 0-30 min, and then the extent of inhibition towards seven CYP isoforms were examined.Result: CYP2C8, CYP2C9, CYP3A4 were inhibited by bifendate with IC50 value of 49.4, 47.2, 1.11μM, respectively. CYP1A2, CYP2A6, CYP2D6 and CYP2E1 were not inhibited by bifendate. Bifendate showed a competitive, mixed, mixed inhibition with the Ki value of 19.1, 22.0, 1.11μM in CYP2C8, CYP2C9, CYP3A4, respectively. Bifendate showed no time-dependent inhibition on CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6,CYP2E1, CYP3A4.Conclusions: Drug-drug interactions are possible when bifendate is co-administrated with drugs cleared by CYP2C8, CYP2C9, or CYP3A4.