Atorvastatin (INN), marketed under the trade name Lipitor and several others, is a member of the drug class known as statins, used for lowering cholesterol. Atorvastatin inhibits the rate-determining enzyme located in hepatic tissue that produces mevalonate, a small molecule used in the synthesis of cholesterol and other mevalonate derivatives. This lowers the amount of cholesterol produced which in turn lowers the total amount of LDL cholesterol.
With 2006 sales of US$12.9 billion under the brand name Lipitor, it is the largest selling drug in the world.
A similar drug, simvastatin, is available as a cheaper generic alternative.
As with other statins, atorvastatin is a competitive inhibitor of HMG-CoA reductase. Unlike most others, however, it is a completely synthetic compound. HMG-CoA reductase catalyzes the reduction of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate, which is the rate-limiting step in hepatic cholesterol biosynthesis. Inhibition of the enzyme decreases de novo cholesterol synthesis, increasing expression of low-density lipoprotein receptors (LDL receptors) on hepatocytes. This increases LDL uptake by the hepatocytes, decreasing the amount of LDL-cholesterol in the blood. Like other statins, atorvastatin also reduces blood levels of triglycerides and slightly increases levels of HDL-cholesterol.
In clinical trials, adding ezetimibe (Zetia) to Lipitor lowered cholesterol more effectively than Vytorin (ezetimibe + simvastatin).