Fenofibrate

A PPARα agonist that exhibits EC50 of 18 and 30 uM for murine and human PPARα, respectively, in a transactivation assay; reduces both LDL and VLDL levels, as well as increasing HDL levels and reduces triglyceride levels; mainly used to reduce cholesterol levels in people at risk of cardiovascular disease.Hypercholesterolemia Approved(In Vitro):Fenofibrate is a relatively potent inhibitor of CYP2B6 (IC50=0.7±0.2 μM) and CYP2C19 (IC50=0.2±0.1 μM). Fenofibrate is also a moderate inhibitor of CYP2C8 (IC50=4.8±1.7 μM) and CYP2C9 (IC50=9.7 μM). Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity than to PPARα. Fenofibrate is a well-known PPARα agonist, but an in vitro assessment of 209 frequently prescribed drugs and related xenobiotics suggests that Fenofibrate is also a potent inhibitor of cytochrome P450 epoxygenase (CYP)2C. The affinity of Fenofibrate to CYP2C is >10 times higher (EC50=2.39±0.4 μM) than to PPARα (EC50=30 μM). Fenofibrate at a low dose inhibits CYP2C8 activity without PPARα activation.(In Vivo):Daily intake of Fenofibrate at this low dose (10 μg/g/day) inhibits retinal and choroidal neovascularization induced by CYP2C8 overexpression by 29% (P=0.021) and 36% (P=1.2×10 9) respectively.