| Indication |
May be used as primary prevention in individuals with multiple
risk factors for coronary heart disease (CHD) and as secondary
prevention in individuals with CHD to reduce the risk of myocardial
infarction (MI), stroke, angina, and revascularization procedures. May
be used to reduce the risk of cardiovascular events in patients with
acute coronary syndrome (ACS). May be used in the treatment of primary
hypercholesterolemia and mixed dyslipidemia, homozygous familial
hypercholesterolemia, primary dysbetalipoproteinemia, and/or
hypertriglyeridemia as an adjunct to dietary therapy to decrease serum
total and low-density lipoprotein cholesterol (LDL-C), apolipoprotein B
(apoB), and triglyceride concentrations, while increasing high-density
lipoprotein cholesterol (HDL-C) levels. |
| Pharmacodynamics |
Atorvastatin, a selective, competitive HMG-CoA reductase
inhibitor, is used to lower serum total and LDL cholesterol, apoB, and
triglyceride levels while increasing HDL cholesterol. High LDL-C, low
HDL-C and high TG concentrations in the plasma are associated with
increased risk of atherosclerosis and cardiovascular disease. The total
cholesterol to HDL-C ratio is a strong predictor of coronary artery
disease and high ratios are associated with higher risk of disease.
Increased levels of HDL-C are associated with lower cardiovascular risk.
By decreasing LDL-C and TG and increasing HDL-C, atorvastatin reduces
the risk of cardiovascular morbidity and mortality. Atorvastatin has a
unique structure, long half-life, and hepatic selectivity, explaining
its greater LDL-lowering potency compared to other HMG-CoA reductase
inhibitors. |
| Mechanism of action |
Atorvastatin selectively and competitively inhibits the hepatic
enzyme HMG-CoA reductase. As HMG-CoA reductase is responsible for
converting HMG-CoA to mevalonate in the cholesterol biosynthesis
pathway, this results in a subsequent decrease in hepatic cholesterol
levels. Decreased hepatic cholesterol levels stimulates upregulation of
hepatic LDL-C receptors which increases hepatic uptake of LDL-C and
reduces serum LDL-C concentrations. |
| Absorption |
Atorvastatin is rapidly absorbed after oral administration with
maximum plasma concentrations achieved in 1 to 2 hours. The absolute
bioavailability of atorvastatin (parent drug) is approximately 12% and
the systemic availability of HMG-CoA reductase inhibitory activity is
approximately 30%. The low systemic bioavailability is due to
presystemic clearance by gastrointestinal mucosa and first-pass
metabolism in the liver. |
| Volume of distribution |
|
| Protein binding |
98% bound to plasma proteins |
| Metabolism |
Atorvastatin is extensively metabolized to ortho- and
parahydroxylated derivatives and various beta-oxidation products. In
vitro inhibition of HMG-CoA reductase by ortho- and parahydroxylated
metabolites is equivalent to that of atorvastatin. Approximately 70% of
circulating inhibitory activity for HMG-CoA reductase is attributed to
active metabolites. |
| Route of elimination |
Eliminated primarily in bile after hepatic and/or extrahepatic
metabolism. Does not appear to undergo significant enterohepatic
recirculation. Less than 2% of the orally administered dose is recovered
in urine. |
| Half life |
14 hours, but half-life of HMG-CoA inhibitor activity is 20-30 hours due to longer-lived active metabolites |
| Clearance |
Not Available |
| Toxicity |
Generally well-tolerated. Side effects may include myalgia,
constipation, asthenia, abdominal pain, and nausea. Other possible side
effects include myotoxicity (myopathy, myositis, rhabdomyolysis) and
hepatotoxicity. To avoid toxicity in Asian patients, lower doses should
be considered. |
