Tìm theo
Simvastatin
Các tên gọi khác (8 ) :
  • 2,2-Dimethylbutyric acid, 8-ester with (4R,6R)-6-(2-((1S,2S,6R,8S,8ar)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl)ethyl)tetrahydro-4-hydroxy-2H-pyran-2-one
  • MK-733
  • Simvastatin
  • Simvastatina
  • Simvastatine
  • Simvastatinum
  • Synvinolin
  • Zocor
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 79902-63-9
ATC: C10AA01
ĐG : Abbott Laboratories Ltd. , http://www.abbott.com
CTHH: C25H38O5
PTK: 418.5662
Simvastatin is a lipid-lowering agent that is derived synthetically from the fermentation of Aspergillus terreus. It is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl COA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C25H38O5
Phân tử khối
418.5662
Monoisotopic mass
418.271924326
InChI
InChI=1S/C25H38O5/c1-6-25(4,5)24(28)30-21-12-15(2)11-17-8-7-16(3)20(23(17)21)10-9-19-13-18(26)14-22(27)29-19/h7-8,11,15-16,18-21,23,26H,6,9-10,12-14H2,1-5H3/t15-,16-,18+,19+,20-,21-,23-/m0/s1
InChI Key
InChIKey=RYMZZMVNJRMUDD-HGQWONQESA-N
IUPAC Name
(1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate
Traditional IUPAC Name
simvastatin
SMILES
[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)C(C)(C)CC
Độ tan chảy
135-138 °C
Độ hòa tan
Insoluble
logP
4.68
logS
-4.5
pKa (strongest acidic)
14.91
pKa (Strongest Basic)
-2.8
PSA
72.83 Å2
Refractivity
117.68 m3·mol-1
Polarizability
47.85 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
3
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : Simvastatin, the methylated form of lovastatin, is an oral antilipemic agent which inhibits HMG-CoA reductase. Simvastatin is used in the treatment of primary hypercholesterolemia and is effective in reducing total and LDL-cholesterol as well as plasma triglycerides and apolipoprotein B.
Cơ Chế Tác Dụng : Simvastatin is a lipid-lowering agent that is derived synthetically from the fermentation of Aspergillus terreus. It is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl COA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol. [PubChem] Simvastatin is a prodrug in which the 6-membered lactone ring of simvastatin is hydrolyzed in vivo to generate the beta,delta-dihydroxy acid, an active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme. Interference with the activity of this enzyme reduces the quantity of mevalonic acid, a precursor of cholesterol.
Dược Động Học :
▧ Absorption :
Absorption of simvastatin, estimated relative to an intravenous reference dose, in each of two animal species tested, averaged about 85% of an oral dose. In animal studies, after oral dosing, simvastatin achieved substantially higher concentrations in the liver than in non-target tissues. However, because simvastatin undergoes extensive first-pass metabolism, the availability of the drug in the systemic is low. Peak plasma concentration occurs 1.3 - 2.4 hours after administration.
▧ Volume of Distribution :
Simvastatin can cross the blood-brain-barrier.
▧ Protein binding :
Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins.
▧ Metabolism :
Hepatic, simvastatin is a substrate for CYP3A4. The major active metabolites of simvastatin are β-hydroxyacid metabolite and its 6'-hydroxy, 6'-hydroxymethyl, and 6'-exomethylene derivatives
▧ Route of Elimination :
Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces.
▧ Half Life :
3 hours
Độc Tính : The most common adverse reactions that lead to discontinuation of therapy include gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%).
Chỉ Định : For the treatment of hypercholesterolemia and for the reduction in the risk of cardiac heart disease mortality and cardiovascular events. It can also be used in adolescent patients for the treatment of heterozygous familial hypercholesterolemia.
Tương Tác Thuốc :
  • Amiodarone Increased risk of rhabdomyolysis
  • Amprenavir Amprenavir may increase the effect and toxicity of simvastatin. Concomitant therapy is contraindicated.
  • Atazanavir Increased risk of myopathy/rhabdomyolysis
  • Bosentan Bosentan may decrease the serum concentration of simvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if bosentan is initiated, discontinued or dose changed.
  • Carbamazepine Carbamazepine, a p-glycoprotein inducer, may decrease the effect of simvastatin by increasing its efflux. Monitor for changes in the therapeutic and adverse effects of simvastatin if carbamazepine is initiated, discontinued or dose changed.
  • Clarithromycin The macrolide, clarithromycin, may increase the toxicity of the statin, simvastatin.
  • Colchicine Increased risk of rhabdomyolysis with this combination
  • Cyclosporine Possible myopathy and rhabdomyolysis
  • Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if delavirdine is initiated, discontinued or dose changed.
  • Diltiazem Diltiazem may increase the serum concentration of simvastatin. Simvastatin may increase the serum concentration of diltiazem. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
  • Dronedarone Dronedarone is a CYP2D6 inhibitor thus increasing serum concentrations of simvastatin 4-fold. Lower doses of simvastatin and doses should not exceed 20 mg to avoid statin-induced toxicities like myopathy. Consider rosuvastatin as cholesterol lowering therapy as there is no significant interaction between rosuvastatin and dronedarone.
  • Efavirenz Efavirenz may decrease the serum concentration of simvastatin. Monitor for changes in the therapeutic and adverse effects of simvastatin if efavirenz is initiated, discontinued or dose changed.
  • Erythromycin The macrolide, erythromycin, may increase the toxicity of the statin, simvastatin.
  • Etravirine Simvastatin, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to monitor continued efficacy of simvastatin therapy.
  • Fenofibrate Increased risk of myopathy/rhabdomyolysis
  • Fluconazole Increased risk of myopathy/rhabdomyolysis
  • Fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if fosamprenavir is initiated, discontinued or dose changed.
  • Fusidic Acid Increased risk of myopathy/rhabdomyolysis
  • Gemfibrozil Increased risk of myopathy/rhabdomyolysis
  • Imatinib Imatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if imatinib is initiated, discontinued or dose changed.
  • Itraconazole Increased risk of myopathy/rhabdomyolysis
  • Ketoconazole Increased risk of myopathy/rhabdomyolysis
  • Lomitapide Simvastatin plasma concentrations are doubled by lomitapide. To prevent dose related adverse effects such as myopathy and rhabdomyolysis it is recommended to reduce the dose of simvastatin by 50%. See FDA label for additional dosage instructions.
  • Nefazodone Nefazodone may increase the effect and toxicity of simvastatin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of simvastatin if nefazodone is initiated, discontinued or dose changed.
  • Nelfinavir Nelfinavir may increase the effect and toxicity of simvastatin. Concomitant therapy should be avoided.
  • Nevirapine The strong CYP3A4 inducer, nevirapine, may decrase the effect of simvastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of simvastatin if nevirapine is initiated, discontinued or dose changed.
  • Pazopanib Elevated liver enzyme levels may be observed with concomitant therapy with pazopanib. Monitor closely for adverse effects.
  • Quinupristin This combination presents an increased risk of toxicity
  • Ranolazine Ranolazine may increase the serum concentration of simvastatin. Monitor for changes in the therapeutic and adverse effects of simvastatin if ranolazine is initiated, discontinued or dose changed.
  • Rifabutin Rifabutin may decrease the effect of simvastatin by increasing its metabolism. Monitor for changes in the therapeutic effect of simvastatin if rifabutin is initiated, discontinued or dose changed.
  • Rifampicin Rifampin may decrease the effect of simvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if rifampin is initiated, discontinued or dose changed.
  • Saxagliptin Simvastatin is a moderate inhibitor of CYP3A4 and increases AUC of saxagliptin by 12%. Exposure of the active metabolite decreased by 2%. However, these changes in pharmacokinetics are not clinical significant.
  • Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
  • Telithromycin Telithromycin may increase the adverse effects of simvastatin by decreasing its metabolism. Concomitant therapy should be avoided.
  • Ticagrelor Patients receiving more than 40 mg per day of simvastatin may be at increased risk of statin-related adverse effects.
  • Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Simvastatin. Concomitant therapy is contraindicated.
  • Tocilizumab Simvastatin is a CYP3A4 and OATP1B1 substrate. Exposure of simvastatin decreases following administration of tocilizumab.
  • Verapamil Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Simvastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce Simvastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Simvastatin if Verapamil is initiated, discontinued or dose changed.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastain if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Tablet - Oral - 5 mg, 10 mg, 20 mg, 40 mg, 80 mg
Dữ Kiện Thương Mại
Giá thị trường
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    Sản phẩm biệt dược : Statex
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  • Sản phẩm biệt dược : Statinal
  • Công ty : Iapharm
    Sản phẩm biệt dược : Stativer
  • Công ty : Merck & Co
    Sản phẩm biệt dược : Zocor
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00641
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00434
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/16714-681-01
PharmGKB
http://www.pharmgkb.org/drug/PA451363
Wikipedia
http://en.wikipedia.org/wiki/Simvastatin
RxList
http://www.rxlist.com/cgi/generic/simva.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/zoc1500.shtml
Drugs.com
http://www.drugs.com/simvastatin.html
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