Astende (Lazar (Argentina));Cirantan (AstraZeneca (Netherlands));Cresadex (Drugtech (Chile));Crestor (AstraZeneca);Provisacor (AstraZeneca (Italy, Netherlands) );Razel (Glenmark (India));Rosedex (Roux-Ocefa (Argentina));Rosimol (Sandoz (Argentina));Rosumed (Labomed (Chile));Rosustatin (Montpellier (Argentina));Rosuvas (Ranbaxy (India));Rosuvast (Bago (Argentina));Rosvel (Laboratorios Chile (Chile));Rovartal (Roemmers (Argentina));Simestat (Simesa (Italy));Sinlip (Gador (Argentina));Visacor (AstraZeneca (Portugal));Vivacor (AstraZeneca (Brazil));

Rosuvastatin calcium;ZD-4522;

Rosuvastatin is an antilipemic agent that competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reducuase catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step in cholesterol biosynthesis. Rosuvastatin belongs to a class of medications called statins and is used to reduce plasma cholesterol levels and prevent cardiovascular disease.

• Ipr pharmaceuticals inc

• A-S Medication Solutions LLC
• AstraZeneca Inc.
• Bryant Ranch Prepack
• Cardinal Health
• Corden Pharma GmbH
• IPR Pharmaceuticals Inc.
• Lake Erie Medical and Surgical Supply
• Murfreesboro Pharmaceutical Nursing Supply
• Nucare Pharmaceuticals Inc.
• PD-Rx Pharmaceuticals Inc.
• Physicians Total Care Inc.
• Prepak Systems Inc.
• Remedy Repack
• Resource Optimization and Innovation LLC
• Southwood Pharmaceuticals

Synthesis Reference

Not Available

General Reference

Di Napoli P, Taccardi AA, Grilli A, De Lutiis MA, Barsotti A, Felaco M, De Caterina R: Chronic treatment with rosuvastatin modulates nitric oxide synthase expression and reduces ischemia-reperfusion injury in rat hearts. Cardiovasc Res. 2005 Jun 1;66(3):462-71. Pubmed Everett BM, Glynn RJ, MacFadyen JG, Ridker PM: Rosuvastatin in the prevention of stroke among men and women with elevated levels of C-reactive protein: justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER). Circulation. 2010 Jan 5;121(1):143-50. Pubmed Jones SP, Gibson MF, Rimmer DM 3rd, Gibson TM, Sharp BR, Lefer DJ: Direct vascular and cardioprotective effects of rosuvastatin, a new HMG-CoA reductase inhibitor. J Am Coll Cardiol. 2002 Sep 18;40(6):1172-8. Pubmed Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW: Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003 Jul 15;92(2):152-60. Pubmed Kilic E, Kilic U, Matter CM, Luscher TF, Bassetti CL, Hermann DM: Aggravation of focal cerebral ischemia by tissue plasminogen activator is reversed by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor but does not depend on endothelial NO synthase. Stroke. 2005 Feb;36(2):332-6. Pubmed Kosmidou I, Moore JP, Weber M, Searles CD: Statin treatment and 3’ polyadenylation of eNOS mRNA. Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2642-9. Pubmed Laufs U, Gertz K, Dirnagl U, Bohm M, Nickenig G, Endres M: Rosuvastatin, a new HMG-CoA reductase inhibitor, upregulates endothelial nitric oxide synthase and protects from ischemic stroke in mice. Brain Res. 2002 Jun 28;942(1-2):23-30. Pubmed McKillop T: The statin wars. Lancet. 2003 Nov 1;362(9394):1498. Pubmed McTaggart F, Buckett L, Davidson R, Holdgate G, McCormick A, Schneck D, Smith G, Warwick M: Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Am J Cardiol. 2001 Mar 8;87(5A):28B-32B. Pubmed Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM: Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006 Apr 5;295(13):1556-65. Pubmed Stalker TJ, Lefer AM, Scalia R: A new HMG-CoA reductase inhibitor, rosuvastatin, exerts anti-inflammatory effects on the microvascular endothelium: the role of mevalonic acid. Br J Pharmacol. 2001 Jun;133(3):406-12. Pubmed The statin wars: why AstraZeneca must retreat. Lancet. 2003 Oct 25;362(9393):1341. Pubmed Ho RH, Tirona RG, Leake BF, Glaeser H, Lee W, Lemke CJ, Wang Y, Kim RB: Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806. Epub 2006 Mar 6. Pubmed

Type	small molecule

Classes

Not Available

Substructures

Not Available

hyperlipidemi 高血脂;

Indication	Used as an adjunct to dietary therapy to treat primary hypercholesterolemia (heterozygous familial and nonfamilial), mixed dyslipidemia and hypertriglyceridemia. Also indicated for homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies or when other such therapies are not available.
Pharmacodynamics	Rosuvastatin is a synthetic, enantiomerically pure antilipemic agent. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.
Mechanism of action	Rosuvastatin is a competitive inhibitor of HMG-CoA reductase. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis. Rosuvastatin acts primarily in the liver. Decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increases hepatic uptake of LDL. Rosuvastatin also inhibits hepatic synthesis of very low density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL. In vitro and in vivo animal studies also demonstrate that rosuvastatin exerts vasculoprotective effects independent of its lipid-lowering properties. Rosuvastatin exerts an anti-inflammatory effect on rat mesenteric microvascular endothelium by attenuating leukocyte rolling, adherence and transmigration (PMID: 11375257). The drug also modulates nitric oxide synthase (NOS) expression and reduces ischemic-reperfusion injuries in rat hearts (PMID: 15914111). Rosuvastatin increases the bioavailability of nitric oxide (PMID: 11375257, 12031849, 15914111) by upregulating NOS (PMID: 12354446) and by increasing the stability of NOS through post-transcriptional polyadenylation (PMID: 17916773). It is unclear as to how rosuvastatin brings about these effects though they may be due to decreased concentrations of mevalonic acid.
Absorption	Bioavailability is approximately 20%
Volume of distribution	134 L
Protein binding	90% bound to plasma proteins (mostly albumin)
Metabolism	Not extensively metabolized. Only ~10% is excreted as metabolite. Cytochrome P450 (CYP) 2C9 is primarily responsible for the formation of rosuvastatin's major metabolite, N-desmethylrosuvastatin. N-desmethylrosuvastatin has approximately 50% of the pharmacological activity of its parent compound in vitro. Rosuvastatin accounts for greater than 87% of the pharmacologic action. Inhibitors of CYP2C9 increase the AUC by less than 2-fold. This interaction does not appear to be clinically significant. Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us. Substrate Enzymes Product Rosuvastatin Cytochrome P450 2C9 Rosuvastatin 5 S-lactone Details Rosuvastatin Cytochrome P450 2C9 Cytochrome P450 2C19 N-Desmethylrosuvastatin Details
Route of elimination	Rosuvastatin is not extensively metabolized; approximately 10% of a radiolabeled dose is recovered as metabolite. Following oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%).
Half life	19 hours
Clearance	Not Available
Toxicity	Generally well-tolerated. Side effects may include myalgia, constipation, asthenia, abdominal pain, and nausea. Other possible side effects include myotoxicity (myopathy, myositis, rhabdomyolysis) and hepatotoxicity. To avoid toxicity in Asian patients, lower doses should be considered. Pharmacokinetic studies show an approximately two-fold increase in peak plasma concentration and AUC in Asian patients (Philippino, Chinese, Japanese, Korean, Vietnamese, or Asian-Indian descent) compared to Caucasians patients.
Affected organisms	Humans and other mammals
Pathways	Pathway Name SMPDB ID Rosuvastatin Pathway SMP00092

Properties
State	solid
Experimental Properties	Property Value Source water solubility Sparingly soluble in water Not Available logP 2.4 Not Available
Predicted Properties	Property Value Source water solubility 8.86e-02 g/l ALOGPS logP 1.47 ALOGPS logP 1.92 ChemAxon logS -3.7 ALOGPS pKa (strongest acidic) 4 ChemAxon pKa (strongest basic) -2.8 ChemAxon physiological charge -1 ChemAxon hydrogen acceptor count 8 ChemAxon hydrogen donor count 3 ChemAxon polar surface area 140.92 ChemAxon rotatable bond count 9 ChemAxon refractivity 121.44 ChemAxon polarizability 48.55 ChemAxon

Drug	Interaction
Colchicine	Increased risk of rhabdomyolysis with this combination
Cyclosporine	Cyclosporine may increase the serum concentration of rosuvastatin. Limit rosuvastatin dosing to 5 mg/day and monitor for changes in the therapeutic and adverse effects of rosuvastatin if cyclosporine is initiated, discontinued or dose changed.
Fenofibrate	May cause additive myotoxicity. Monitor for symptoms of muscle toxicity during concomitant therapy.
Gemfibrozil	Gemfibrozil may increase the therapeutic and toxic effects of rosuvastatin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of rosuvastatin if gemfibrozil is initiated, discontinued or dose changed.
Magnesium	Magnesium-containing antacids may decrease the absorption of rosuvastatin.
Tipranavir	Concomitant therapy of Rosuvastatin and Tipranavir/Ritonavir may increase Rosuvastatin and Tipranavir concentrations. Consider alternate therapy.

Not Available