In Vitro Human Cytochrome P450 Isozymes (CYPs) Inhibition of Epifriedelanol on CYP2C9, CYP2E1 and CYP3A4

Epifriedelanol is the main ingredient of expectorant in Aster tataricus and was newly found with diverse pharmacological activities. In vitro CYP450 inhibition of epifriedelanol was evaluated using human liver microsomes (HLMs) to understand their drug-drug interaction potential. CYP450 isoform-specific substrates of CYP1A2, CYP3A4, CYP2A6, CYP2E1, CYP2D6, CYP2C9, CYP2C19, and CYP2C8 were incubated in HLMs with or without epifriedelanol. Preliminary CYP450 inhibition (IC (50)) data were generated for each of these isoforms. The type of inhibition and estimation of the inhibition constants (K (i)) of CYP3A4, CYP2E1, and CYP2C9 were determined. Epifriedelanol was inhibitors of CYP3A4, CYP2E1, and CYP2C9, with IC (50) of 66.13, 24.77, and 9.31 mu M, respectively. Epifriedelanol exhibited competitive inhibition of CYP2E1 and CYP2C9 activity and the K (i) were found to be 11.41 and 4.518 mu M, respectively. Epifriedelanol exhibited non-competitive and time-dependent inhibition of CYP3A4 activity, and the K (i) was found to be 30.30.m, K (I)/ K (inact) was 33.65/0.108 mu M/min. Epifriedelanol may lead to significant clinical adverse drug interactions upon coadministration of drugs that are substantially metabolized by CYP3A4, CYP2E1, or CYP2C9.