2-[4-(4-Chlorbenzoyl)phenoxy]-2-methylpropionsure

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Metabolite of Fenofibrate

Positive

0.21

2.7

Agilent XCT

Electrospray ionization

formic acid (5.3nM)

Warning

H302 (99%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P273, P301+P317, P330, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 96 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Fenofibric acid

vLess-DILI-concern

2

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

Various clinical studies have shown that elevated levels of total cholesterol, low-desnsity-lipoprotein (LDL-C), and apolipoprotein B (apo B) - an LDL membrane complex - are associated with human atherosclerosis. Concurrently, decreased levels of high-density-lioprotein (HDL-C) and its transport complex, apolipoproteins apo AI and apo AII, are associated with the development of atherosclerosis. Furthermore, epidemiological investigations demonstrate that cardiovascular morbidity and mortality vary directly with the levels of total cholesterol, LDL-C, and triglycerides, and inversely with the level of HDL-C. Fenofibric acid, the active metabolite of fenofibrate, subsequently produces reductions in total cholesterol, LDL-C, apo B, total triglycerides, and triglyceride rich lipoprotein (VLDL) in treated patients. Moreover, such treatment with fenofibrate also results in increases in HDL-C and apo AI and apo AII.

Having performed clinical studies with in vivo transgenic mice and in vitro human hepatocyte cultures, it is believed that the principal mechanism of action of fenofibric acid is demonstrated through its capability to activate peroxisome proliferator receptor alpha (PPAR-alpha). By activating PPAR-alpha, fenofibric acid increases lipolysis and the elimination of triglyceride-rich particles from plasma by actuating lipoprotein lipase and reducing production of apoprotein C-III, which acts as an inhibitor of lipoprotein lipase activity. The resultant decrease in triglycerides causes an alteration in the size and composition of low-density-lipoprotein from small, dense particles to large, buoyant ones. The size of these larger low-density-lipoprotein particles have a greater affinity for cholesterol receptors and are therefore catabolized more rapidly. Additionally, fenofibric acid's activation of PPAR-alpha also induces an increase in the synthesis of apoproteins apo A-I, apo A-II, and high-density-lipoprotein. Moreover, the use of fenofibric acid can also act to reduce serum uric acid levels in ordinary or hyperuricemic individuals by increasing the urinary excretion of uric acid.

In vitro and in vivo metabolism studies reveal that fenofibric acid does not experience significant oxidative metabolism via the cytochrome P450 isoenzymes. The CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 enzymes are not known to play a role in the metabolism of fenofibric acid. Rather, fenofibric acid is predominantly conjugated with glucuronic acid and then excreted in urine. A small amount of fenofibric acid is reduced at the carbonyl moiety to benzhydrol metabolite which is, in turn, conjugated with glucuronic acid and excreted in urine.

Fenofibric Acid has known human metabolites that include Fenofibryl glucuronide.

BGF9MN2HU1

FENOFIBRIC ACID

Established Pharmacologic Class [EPC] - Peroxisome Proliferator Receptor alpha Agonist

Fenofibric acid is a Peroxisome Proliferator Receptor alpha Agonist.

FENOFIBRIC ACID

Peroxisome Proliferator Receptor alpha Agonist [EPC]

Substances used to lower plasma CHOLESTEROL levels.

Substances that lower the levels of certain LIPIDS in the BLOOD. They are used to treat HYPERLIPIDEMIAS.

Some studies have demonstrated that the bioavailability of fenofibric acid (a sample administration of 130 mg oral suspension to healthy volunteers about 4 hours after a light breakfast) is approximately 81% in the stomach, 88% in the proximal small bowel, 84% in the distal small bowel, and 78% in the colon. Nevertheless, following the oral administration of fenofibric acid in healthy volunteers, median peak plasma levels for the drug occurred about 2.5 hours after administration. Moreover, exposure after administration of three 35 mg fenofibric acid tablets is largely comparable to that of one 105 mg tablet.

Fenofibric acid metabolites are largely excreted in the urine.

The volume of distribution for fenofibric acid is demonstrated to be 70.9 +/- 27.5 L.

In five elderly volunteers aged 77 to 87, the oral clearance of fenofibric acid after a single oral dose of fenofibrate was 1.2 L/h, which compares to 1.1 L/h in young adults.