HMG-CoA reductase inhibitor; inhibits rate-limiting step in cholesterol biosynthesis by competitively inhibiting HMG-CoA reductase

Bioavailability: 14% (parent drug)

Onset: 3-5 days

Duration: 48-72 hr

Peak serum time: 1-2 hr

Maximum effect: 2 weeks

Protein bound: 98%

Vd: 381 L

Via hepatic P450 enzyme CYP3A4

Metabolites: Ortho- and parahydroxylated derivatives and beta-oxidation product (inactive)

Half-life: 14 hr

Dialyzable: No (HD)

Excretion: Mainly via bile; urine (2%)

SLCO1B1 (OATP1B1) CC genotype significantly increases AUCs of parent drug and metabolites compared with the CT or TT genotypes

This polymorphism is proposed to reduce transport into the liver, the main site of statin metabolism and elimination

SLCO1B1 polymorphism is thought to have a lesser effect on the more hydrophilic statins (eg, rosuvastatin, fluvastatin) compared with those that are more lipophilic (eg, atorvastatin, simvastatin)

Other genetic polymorphisms of elimination (eg, CYP450, P-glycoprotein) for each individual drug must also be considered, to explain variability for statin clearance among patients that exhibit SCLO1B1 polymorphism

SLCO1B1 CC genotype is most common in Caucasians and Asians (15%)

Risk of myopathy is 2.6- to 4.3-fold higher if the C allele is present and 16.9-fold higher in CC homozygotes than in TT homozygotes