Drugs that Regulate Lipoprotein Metabolism

Lipoproteins, differentiated on the basis of density, size, and protein content, are essential for the biogenesis of plasma membrane and maintenance of its integrity; they also serve as sources of energy, hormone precursors, and signaling molecules.3 In blood, lipoproteins transport cholesterol and triglycerides. Abnormalities of lipoprotein metabolism appear to be the result of genetic factors, which modify the sensitivity of individuals to adverse dietary habits and to sedentary lifestyles.

Elevated cholesterol-rich low-density lipoproteins (LDLs) and lipoproteins that are rich in triglycerides (TGs), and decreased levels of high-density lipoproteins (HDLs) are strongly associated with atherosclerosis.3 Diet and exercise can reduce total plasma cholesterol concentrations by as much as 25%. If this approach is insufficient to normalize lipid levels drug therapy is initiated. Drugs in the top 300 that regulate lipoprotein metabolism (Table 1) fall into six major classes.2,3,10

Table 1. Drugs that Affect Cholesterol and Lipoprotein Metabolism.2,3,10
Drugs Mechanisms of Action Common Indications
Inhibitors of cholesterol synthesis
  • Atorvastatin
  • Simvastatin
  • Pravastatin
  • Rosuvastatin
  • Lovastatin
Inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis
  • Decrease LDL
  • Decrease TG
  • Increase HDL
  • Hypercholesterolemia
  • Prophylaxis for coronary atherosclerosis
Inhibitors of bile acid absorption
  • Colestipol
Bind to bile acids and prevent enterohepatic circulation
  • Decrease LDL
  • Increase HDL
  • Hypercholesterolemia
Inhibitors of cholesterol absorption
  • Ezetimibe
  • Ezetimibe w/simvastatin
Decrease cholesterol transport into enterocytes
  • Decrease LDL
  • Decrease TG
  • Increase HDL
  • Hypercholesterolemia
Fibrates
  • Fenofibrate
  • Gemfibrozil
Agonists of peroxisome proliferator-activated receptor α (PPARα) in hepatocytes
  • Decrease TG
  • Decrease LDL
  • Increase HDL
  • Hypertriglyceridemia
Niacin
  • Niacin
  • Niacin w/simvastatin
Reduces free fatty acid release from adipose tissue
  • Decreases TG
  • Decreases LDL
  • Increases HDL
  • Hypertriglyceridemia
  • Hypercholesterolemia
Omega-3 fatty acids
  • Omega-3-acid ethyl ester
Regulate hepatic nuclear transcription factors to reduce TG synthesis and increase fatty acid oxidation
  • Reduces TG
  • Hypertriglyceridemia