Rosuvastatin: A New HMG-CoA Reductase Inhibitor for the Treatment of Hypercholesterolemia

Abstract

Because of their excellent tolerability and their positive impact on lipid parameters, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have become the drugs of first choice for many patients with dyslipidemia. Rosuvastatin is an investigational statin in the U.S. with a number of favorable characteristics, which include low lipophilicity, high hepatocyte selectivity, minimal metabolism, and a low propensity for cytochrome P450 drug interactions. Rosuvastatin has been studied at doses ranging from 1 to 80 mg. In comparative clinical trials, rosuvastatin given at 5 to 10 mg/day reduced low-density lipoprotein cholesterol to a significantly greater extent than atorvastatin 10 mg/day, pravastatin 20 mg/day, and simvastatin 20 mg/day. In addition, rosuvastatin exhibited beneficial effects on other lipid parameters such as high-density lipoprotein cholesterol and triglycerides. Rosuvastatin's safety profile was demonstrated to be similar to those of other statins. Given its favorable pharmacokinetic and pharmacodynamic characteristics, rosuvastatin is likely to become a valuable addition to the statin drug class. The author reviews the pharmacologic and pharmacokinetic properties of this new statin.

Effect of Atorvastatin Versus Rosuvastatin on Levels of Serum Lipids, Inflammatory Markers and Adiponectin in Patients with Hypercholesterolemia

“…Atorvastatin has more powerful antiinflammatory and lipid-lowering effects than simvastatin, pravastatin, and lovastatin (13). However, rosuvastatin, a relatively new HMG-CoA reductase inhibitor, has a number of favorable characteristics, including low lipophilicity, high hepatocyte selectivity, minimal metabolism, and a low propensity for cytochrome P450 drug interactions (14). The present study comparing the two statins found both with favorable effects on lipid modulation, but 10 mg rosuvastatin in particular lowered serum TC and LDL-C levels to a greater extent in patients with hypercholesterolemia.…”

Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production

“…These agents lower lipid levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis, and are known to reduce cardiovascular morbidity and mortality in diabetic patients (13,14). Statins improve cardiovascular function in IR both indirectly via effects on blood elements such as triglycerides, cholesterol, and low-density lipoproteins (5,28) and by direct effects on the vasculature. These direct effects include the facilitation of endothelial nitric oxide (NO) production (12,16,41) and reduction of oxidative stress in the vessel wall (25,34,39).…”

Effects of rosuvastatin on the production and activation of matrix metalloproteinase-2 and migration of cultured rat vascular smooth muscle cells induced by homocysteine

“…Specific non-lipid lowering effects of statins include antioxidant properties, maintenance of atherosclerotic plaque stabilization, antiinflammatory action, modulation of endothelial function, and anti-proliferation of VSMCs (Arnaboldi et al, 2007;Puccetti et al, 2007). Rosuvastatin, a relatively new HMG-CoA reductase inhibitor, has a lot of favorable characteristics, such as low lipophilicity, high hepatocyte selectivity, minimal metabolism, and a low propensity for cytochrome P450 drug interactions (Cheng-Lai, 2003). So, could the pleiotropic statin, rosuvastatin, reduce the homocysteine-induced excessive expression and activation of MMP-2 and abnormal cell migration of VSMCs?…”