Roswin Mechanism of Action

HMG-CoA reductase inhibitor.
Pharmacology: Pharmacodynamics: Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. In vivo studies in animals and in vitro studies in cultured animal and human cells have shown rosuvastatin to have a high uptake into, and selectivity for, action in the liver, the target organ for cholesterol lowering.
Rosuvastatin exerts its lipid-modifying effects by increasing the number of hepatic low density lipoprotein (LDL) receptors on the cell surface, thus enhancing uptake and catabolism of LDL and by inhibiting the hepatic synthesis of very low density lipoprotein (VLDL), thereby reducing the total VLDL and LDL particles.
Studies have shown that HMG-CoA reductase inhibitors decrease non-high density lipoprotein (non-HDL), i.e., all circulating cholesterol not in HDL, and apolipoprotein B (Apo B) or reduce the Apo B/Apo A-I ratio.
Pharmacokinetics: Peak rosuvastatin plasma concentrations are reached 3 to 5 hours after oral administration. Both peak concentration (C_max) and area under the plasma concentration-time curve (AUC) increase in direct proportion to rosuvastatin dose. The absolute bioavailability of rosuvastatin is approximately 20%.
Administration of rosuvastatin with food did not affect rosuvastatin AUC.
Rosuvastatin AUC does not differ after morning or evening drug administration.
Rosuvastatin's mean volume of distribution at steady-state is about 134 L. Rosuvastatin is 88% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations.
Rosuvastatin is not extensively metabolized; about 10% of a radiolabeled dose is recovered as metabolite. The major metabolite is N-desmethyl rosuvastatin, which is formed principally by cytochrome P450 2C9, in vitro studies have demonstrated that N-desmethyl rosuvastatin has approximately one-sixth to one-half the HMG-CoA reductase inhibitory activity of rosuvastatin. Overall, more than 90% of active plasma HMG-CoA reductase inhibitory activity is accounted for by rosuvastatin.
Rosuvastatin and its metabolites are primarily excreted in the feces (90%) after oral administration. The elimination half-life (t_½) is about 19 hours.
Pharmacokinetic studies demonstrate an approximate 2-fold increase in median exposure (AUC and C_max) in Asian subjects (having either Vietnamese, Filipino, Chinese, Japanese, Korean, or Asian-Indian origin) compared with Caucasians. A population pharmacokinetic analysis showed no clinically relevant differences in pharmacokinetics among Caucasians, Hispanic and Black or Afro-Caribbean groups (see Precautions).