Atorvastatin

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	381 L
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. Enzyme Metabolite Reaction Km Vmax Cytochrome P450 3A5 para-hydroxyatorvastatin hydroxylation Cytochrome P450 3A5 ortho-hydroxyatorvastatin hydroxylation Cytochrome P450 3A4 para-hydroxyatorvastatin hydroxylation 0 0 Cytochrome P450 3A4 ortho-hydroxyatorvastatin hydroxylation 0 0 Cytochrome P450 2C8 para-hydroxyatorvastatin hydroxylation
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.
Affected organisms	Humans and other mammals