clofibrate

Clofibrate is a lipid-lowering medication in the fibrate class. It was developed in the 1960s and was used to treat hyperlipidemia, particularly marked elevations in triglycerides and mixed dyslipidemia. In many countries it has been largely replaced by newer fibrates and is now rarely used.

Clofibrate acts as a ligand of peroxisome proliferator-activated receptor alpha (PPAR‑α), which regulates the expression of genes involved in fatty acid oxidation and lipoprotein metabolism. Activation of PPAR‑α increases lipoprotein lipase activity, reduces hepatic production of very‑low‑density lipoprotein (VLDL), and enhances clearance of triglyceride‑rich lipoproteins. The result is lower serum triglycerides and, to a lesser extent, a modest increase in high‑density lipoprotein (HDL) cholesterol.

Clofibrate is administered by mouth. It is metabolized in the liver and excreted in the urine. Dosing regimens and duration vary by region and clinical indication; detailed recommendations are provided in product labeling and clinical guidelines.

Safety considerations include gastrointestinal disturbances, liver enzyme elevations, and an increased risk of gallstone formation. Animal studies raised concerns about carcinogenic potential, which contributed to its withdrawal or restricted use in several markets. Drug interactions have been reported, including an increased risk of myopathy when combined with statins and potential effects on coagulation with anticoagulants.

Clofibrate is largely considered obsolete for routine dyslipidemia management in favor of other fibrates with more favorable safety profiles.