![]() ![]() ![]() Įxcretion: Statins are extensively metabolized, and the amount of statin excreted in its unchanged form through renal elimination is comparatively less. Atorvastatin and lovastatin are both substrates and inhibitors of P-gp(permeability glycoprotein). OATPB1(organic anion-transporting polyprotein) plays a role in eliminating atorvastatin, rosuvastatin, simvastatin, pitavastatin, and pravastatin, while OATPB3 is involved in the elimination of rosuvastatin, fluvastatin, and pravastatin. Rosuvastatin is metabolized(to a lesser degree) by CYP2C9 and CYP2C19. Metabolism: CYP3A4 plays a crucial role in the metabolism of atorvastatin, lovastatin, and simvastatin. Hydrophilic statins pravastatin and to and rosuvastatin are attached to the polar surface of the cell membrane and require protein transporters to enter the cell to inhibit the HMG-CoA reductase. Lipophilic statins can penetrate cells by passive diffusion and are widely distributed in different tissues. All statins have high plasma protein binding(PPB) except pravastatin(PPB ~50%). ĭistribution: Protein binding affects drug distribution and the pharmacological efficacy of drugs because only the unbound or free drug can elicit targeted effects. Simvastatin and lovastatin are prodrugs converted to an active form by hydrolysis. The bioavailability of pitavastatin is highest (>60%), followed by rosuvastatin(20%), while simvastatin has <5% bioavailability. Atorvastatin is completely absorbed after oral administration, but atorvastatin undergoes extensive first-pass metabolism hence the bioavailability is about 12%. Ībsorption: Absorption is faster for lipophilic drugs like atorvastatin, simvastatin, fluvastatin, pitavastatin, and lovastatin than hydrophilic statins like rosuvastatin or pravastatin. The COSMOS (coronary atherosclerosis Study measuring the effects of rosuvastatin using intravascular ultrasound in Japanese subjects) trial results indicated that patients treated with rosuvastatin had a substantial decrease in plaque volume independent of LDL-C reduction. This pleiotropic effect is the class effect of statins and is demonstrated by all statins. ![]() In addition, they promote plaque stability and prevent platelet aggregation. Consequently, statins have anti-inflammatory, antioxidant, antiproliferative, and immunomodulatory effects. Statins inhibit the synthesis of isoprenoid intermediates required for activating intracellular/signaling proteins(Ras, Rho, Rab, Rac, Ral, or Rap). HMG CoA reductase inhibitors have pleiotropic effects. The RhoA gene may play an important role in statin's LDL-C response. Drug responses may also differ according to genetic factors, such as the ATP binding cassette G2, lipoprotein(a), and apo E genes. Statin treatment reduces the hepatic production rate of apo B100 containing lipoproteins, leading to a decrease in both cholesterol and triglyceride concentrations. By reducing hepatic cholesterol synthesis, an upregulation of LDL receptors and increased hepatic uptake of LDL-cholesterol from the circulation occurs. Statins are a selective, competitive inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, the enzyme responsible for converting HMG-CoA to mevalonate in the cholesterol synthesis pathway. ![]()
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