Tìm theo
Rosuvastatin
Các tên gọi khác (2) :
  • (3R,5S,6e)-7-(4-(4-Fluorophenyl)-6-(1-methylethyl)-2-(ethyl(methylsulfonyl)amino)-5-pyrimidinyl)-3,5-dihydroxy-6-heptenoic acid
  • (3R,5S,6e)-7-{4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl}-3,5-dihydroxyhept-6-enoic acid
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 287714-41-4
ATC: C10AA07
ĐG : A-S Medication Solutions LLC , http://orders.a-smeds.com
CTHH: C22H28FN3O6S
PTK: 481.538
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C22H28FN3O6S
Phân tử khối
481.538
Monoisotopic mass
481.168284538
InChI
InChI=1S/C22H28FN3O6S/c1-13(2)20-18(10-9-16(27)11-17(28)12-19(29)30)21(14-5-7-15(23)8-6-14)25-22(24-20)26(3)33(4,31)32/h5-10,13,16-17,27-28H,11-12H2,1-4H3,(H,29,30)/b10-9+/t16-,17-/m1/s1
InChI Key
InChIKey=BPRHUIZQVSMCRT-VEUZHWNKSA-N
IUPAC Name
(3R,5S,6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid
Traditional IUPAC Name
rosuvastatin
SMILES
CC(C)C1=NC(=NC(C2=CC=C(F)C=C2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(=O)O)N(C)S(C)(=O)=O
Độ hòa tan
Sparingly soluble in water
logP
0.13
logS
-3.7
pKa (strongest acidic)
4
pKa (Strongest Basic)
-2.8
PSA
140.92 Å2
Refractivity
121.44 m3·mol-1
Polarizability
48.55 Å3
Rotatable Bond Count
9
H Bond Acceptor Count
8
H Bond Donor Count
3
Physiological Charge
-1
Number of Rings
2
Bioavailability
1
Rule of Five
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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. 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.
Dược Động Học :
▧ Absorption :
Bioavailability is approximately 20%. Peak plasma concentrations were reached 3 to 5 hours following oral dosing. Both Cmax and AUC increased in approximate proportion to CRESTOR dose. Food has no effect on the AUC of rosuvastatin.
▧ Volume of Distribution :
* 134 L [steady-state]
▧ Protein binding :
88% bound to plasma proteins (mostly albumin). Binding is reversible and independent of plasma concentrations.
▧ 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 clearance is not dependent on metabolism by cytochrome P450 3A4 to a clinically significant extent. Rosuvastatin accounts for greater than 90% of the pharmacologic action. Inhibitors of CYP2C9 increase the AUC by less than 2-fold. This interaction does not appear to be clinically significant.
▧ 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%). After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route.
▧ Half Life :
19 hours
Độc Tính : 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.
Chỉ Định : Used as an adjunct to dietary therapy to treat primary hyperlipidemia (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. Furthermore, it is used to slow the progression of atherosclerosis and for primary prevention of cardiovascular disease.
Tương Tác Thuốc :
  • 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.
Liều Lượng & Cách Dùng : Tablet - Oral - 5 mg, 10 mg, 20 mg, 40 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Crestor 5 mg Tablet
    Giá bán buôn : USD >1.45
    Đơn vị tính : tablet
  • Biệt dược thương mại : Crestor 10 mg Tablet
    Giá bán buôn : USD >1.53
    Đơn vị tính : tablet
  • Biệt dược thương mại : Crestor 20 mg Tablet
    Giá bán buôn : USD >1.91
    Đơn vị tính : tablet
  • Biệt dược thương mại : Crestor 40 mg Tablet
    Giá bán buôn : USD >2.24
    Đơn vị tính : tablet
  • Biệt dược thương mại : Crestor 10 mg tablet
    Giá bán buôn : USD >4.68
    Đơn vị tính : tablet
  • Biệt dược thương mại : Crestor 5 mg tablet
    Giá bán buôn : USD >4.68
    Đơn vị tính : tablet
  • Biệt dược thương mại : Crestor 20 mg tablet
    Giá bán buôn : USD >4.69
    Đơn vị tính : tablet
  • Biệt dược thương mại : Crestor 40 mg tablet
    Giá bán buôn : USD >4.7
    Đơn vị tính : tablet
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01098
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D01915
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50215703
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0310-0755-90
PharmGKB
http://www.pharmgkb.org/drug/PA134308647
Wikipedia
http://en.wikipedia.org/wiki/Rosuvastatin
RxList
http://www.rxlist.com/cgi/generic/crestor.htm
Drugs.com
http://www.drugs.com/cdi/rosuvastatin.html
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