| Indication | For treatment of adult patients with very high elevations of serum triglyceride levels (types IV and V hyperlipidemia) who are at risk of developing pancreatitis (inflammation of the pancreas) and who do not respond adequately to a strict diet. |
| Pharmacodynamics | Gemfibrozil, a fibric acid antilipemic agent similar to clofibrate, is used to treat hyperlipoproteinemia and as a second-line therapy for type IIb hypercholesterolemia. It acts to reduce triglyceride levels, reduce VLDL levels, reduce LDL levels (moderately), and increase HDL levels (moderately). |
| Mechanism of action | Gemfibrozil increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. It does so by activating Peroxisome proliferator-activated receptor-alpha (PPARĪ±) 'transcription factor ligand', a receptor that is involved in metabolism of carbohydrates and fats, as well as adipose tissue differentiation. This increase in the synthesis of lipoprotein lipase thereby increases the clearance of triglycerides. Chylomicrons are degraded, VLDLs are converted to LDLs, and LDLs are converted to HDL. This is accompanied by a slight increase in secretion of lipids into the bile and ultimately the intestine. Gemfibrozil also inhibits the synthesis and increases the clearance of apolipoprotein B, a carrier molecule for VLDL. |
| Absorption | Well absorbed from gastrointestinal tract (within 1-2 hours). |
| Volume of distribution | Not Available |
| Protein binding | 95% |
| Metabolism | Hepatic. Gemfibrozil mainly undergoes oxidation of a ring methyl group to successively form a hydroxymethyl and a carboxyl metabolite. |
| Route of elimination | Approximately seventy percent of the administered human dose is excreted in the urine, mostly as the glucuronide conjugate, with less than 2% excreted as unchanged gemfibrozil. |
| Half life | 1.5 hours |
| Clearance | Not Available |
| Toxicity | Oral, mouse: LD50 = 3162 mg/kg. Symptoms of overdose include abdominal cramps, diarrhea, joint and muscle pain, nausea, and vomiting. |