Absorption<unk>  undergoes rapid absorption when taken orally, with an approximate time to maximum plasma concentration (Tmax) of 1–2 h. The absolute bioavailability of the medication is about 14%, but the systemic availability for HMG-CoA reductase activity is approximately 30%.<unk>  undergoes high intestinal clearance and first-pass metabolism, which is the main cause for the low systemic availability. Administration of<unk>  with food produces a 25% reduction in Cmax (rate of absorption) and a 9% reduction in AUC (extent of absorption), although food does not affect the plasma LDL-C-lowering efficacy of<unk> . Evening dose administration is known to reduce the Cmax and AUC by 30% each. However, time of administration does not affect the plasma LDL-C-lowering efficacy of<unk> . Distribution The mean volume of distribution of<unk>  is approximately 381 L. It is highly protein bound (≥98%), and studies have shown it is likely secreted into human breastmilk. Metabolism<unk>  metabolism is primarily through cytochrome P450 3A4 hydroxylation to form active ortho- and parahydroxylated metabolites, as well as various beta-oxidation metabolites. The ortho- and parahydroxylated metabolites are responsible for 70% of systemic HMG-CoA reductase activity. The ortho-hydroxy metabolite undergoes further metabolism via glucuronidation. As a substrate for the CYP3A4 isozyme, it has shown susceptibility to inhibitors and inducers of CYP3A4 to produce increased or decreased plasma concentrations, respectively. This interaction was tested in vitro with concurrent administration of erythromycin, a known CYP3A4 isozyme inhibitor, which resulted in increased plasma concentrations of<unk> . It is also an inhibitor of cytochrome 3A4. Excretion<unk>  is primarily eliminated via hepatic biliary excretion, with less than 2% recovered in the urine. Bile elimination follows hepatic and/or extrahepatic metabolism. There does not appear to be any entero-hepatic recirculation.<unk>  has an approximate elimination half-life of 14 hours. Noteworthy, the HMG-CoA reductase inhibitory activity appears to have a half-life of 20–30 hours, which is thought to be due to the active metabolites.<unk>  is also a substrate of the intestinal P-glycoprotein efflux transporter, which pumps the medication back into the intestinal lumen during medication absorption. In hepatic insufficiency, plasma concentrations of<unk>  are significantly affected by concurrent liver disease. People with Child-Pugh Stage A liver disease show a four-fold increase in both Cmax and AUC. People with Child Pugh stage B liver disease show a 16-fold increase in Cmax and an 11-fold increase in AUC. Geriatric people (>65years old) exhibit altered pharmacokinetics of<unk>  compared to young adults, with mean AUC and Cmax values that are 40% and 30% higher, respectively. Additionally, healthy elderly people show a greater pharmacodynamic response to<unk>  at any dose; therefore, this population may have lower effective doses.
Atorvastatin
Clofibrate
Simvastatin
Fenofibrate
Lovastatin
Ezetimibe
Fluvastatin
Pravastatin