Gemfibrozil is a synthetic antihyperlipidemic agent which is structurally related to clofibrate. It has been shown to be 10 times as potent in reducing triglycerides in animal studies and 3 times more potent than active clofibrate in reducing platelet aggregation.
Preliminary studies in human volunteers indicate that gemfibrozil is a safe and effective antihyperlipidemic agent in selected cases of primary hyperlipidemia.
Pharmacology: Gemfibrozil is a lipid-regulating agent which lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total serum cholesterol. These decreases occur primarily in the very low-density lipoprotein (VLDL) fraction. It has been reported that gemfibrozil may increase levels of high-density lipoprotein (HDL) subfractions, HDL2 and HDL3 as well as apolipoproteins A-I and A-II.
The mechanism of action of gemfibrozil is not completely understood but may involve inhibition of peripheral lipolysis; reduced hepatic extraction of free fatty acids which reduces hepatic triglyceride production; inhibition of synthesis and increased clearance of VLDL carrier; apolipoprotein B, which also reduces VLDL production; and according to animal studies, reduced incorporation of long-chain fatty acids into newly formed triglycerides accelerated turnover and removal of cholesterol from the liver (stimulates incorporation of cholesterol precursors into liver sterols), and increased excretion of cholesterol in the feces.
Pharmacokinetics: Gemfibrozil is well absorbed from the intestinal tract after oral administration. Peak plasma levels occur in 1-2 hrs with a plasma half-life of 1.5 hrs following single dose and 1.3 hrs following multiple doses. Plasma levels appear proportional to dose and do not demonstrate accumulation over time following multiple doses.
Gemfibrozil mainly undergoes oxidation of a ring methyl group to successively form a hydroxymethyl and carboxyl metabolite. Approximately 70% of the human dose is excreted in the urine, mostly of the glucuronide conjugate, with <2% excreted as unchanged gemfibrozil. Six percent of the dose is accounted for in the feces.
Capsule: Unlike clofibrate, gemfibrozil has no effect on plasma fibrinogen, nor does it influence glucose tolerance.