Torus-10/Torus-20 Mechanism of Action

HMG-CoA Reductase Inhibitor.
Pharmacology: Pharmacodynamics: Rosuvastatin is a 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor indicated for the treatment of hyperlipidemia. Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase. HMG-CoA reductase is a rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor for cholesterol. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering. It differs structurally from other statins, containing a polar methane sulphonamide group which confers relative hydrophilicity period. The relative hydrophilicity of rosuvastatin imparts greater selectivity for uptake into hepatic versus nonhepatic cells. Rosuvastatin increases the number of hepatic LDL receptors on the cell-surface, enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles. In preclinical studies, the potency of rosuvastatin has been found to be greater than that of other statins (i.e. atorvastatin, simvastatin, pravastatin, lovastatin, cerivastatin, and fluvastatin). Rosuvastatin reduces elevated LDL-cholesterol, total cholesterol and triglycerides and increases HDL-cholesterol. It also lowers ApoB, nonHDL-C, VLDL-C, VLDL-TG and increases ApoA-I. It also lowers the LDL-C/HDL-C, total C/HDL-C and nonHDL-C/HDL-C and the ApoB/ApoA-I ratios.
Pharmacokinetics: Rosuvastatin is incompletely absorbed from the gastrointestinal tract, with a bioavailability of about 20%. Peak plasma concentrations are achieved about 5 hours after an oral dose. It is taken up extensively by the liver, its primary site of action, and undergoes limited metabolism, mainly by the cytochrome P450 isoenzyme CYP2C9. It is about 90% bound to plasma proteins. The plasma elimination half-life of rosuvastatin is about 19 hours. Approximately 90% of an oral dose of rosuvastatin is excreted in the feces, including absorbed and non-absorbed drug, and the remainder is excreted in the urine; about 5% of a dose is excreted unchanged in urine.