gemfibrozil
Summary
Gemfibrozil is a fibrate class drug that lowers triglycerides by activating PPAR-alpha, which upregulates lipoprotein lipase activity. It is primarily used to treat severe hypertriglyceridemia to reduce the risk of pancreatitis. It also modestly raises HDL levels.
Detail
Gemfibrozil is a fibric acid derivative that acts as a PPAR-alpha agonist. This activation increases the transcription of lipoprotein lipase, enhancing the clearance of triglyceride-rich lipoproteins (VLDL and chylomicrons) from the plasma. It also increases apolipoprotein A-I and A-II production, modestly raising HDL, and decreases hepatic VLDL synthesis.
Clinical use: Gemfibrozil is indicated for severe hypertriglyceridemia (>500 mg/dL) to prevent acute pancreatitis, and can be used in mixed dyslipidemia. It has a lesser effect on LDL compared to statins.
Adverse effects: Myopathy/rhabdomyolysis (risk significantly increased when combined with statins due to CYP interactions - gemfibrozil inhibits statin glucuronidation and OATP1B1-mediated hepatic uptake), cholelithiasis (gallstones) due to increased cholesterol saturation in bile, GI upset, and hepatotoxicity (mild transaminase elevation).
Key Step 1/2 point: Avoid combining gemfibrozil with statins due to markedly increased risk of myopathy/rhabdomyolysis - fenofibrate is preferred if a fibrate-statin combination is needed. Also tested: fibrates are the most effective class for lowering triglycerides, more so than niacin, statins, or fish oil.
Mechanism summary: PPAR-alpha agonist → ↑LPL → ↓VLDL/triglycerides, mild ↑HDL, mild ↓LDL.
Sources
- First Aid for the USMLE Step 1
- Katzung's Basic and Clinical Pharmacology
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- UpToDate: Lipid-lowering drug therapy
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.