用户名： 密   码：
注册 | 忘记密码？
药品详细

Simvastatin(辛伐他汀)

化学结构式图
中文名
辛伐他汀
英文名
Simvastatin
分子式
C25H38O5
化学名
(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
分子量
Average: 418.5662
Monoisotopic: 418.271924326
CAS号
79902-63-9
ATC分类
C10A 未知
药物类型
small molecule
阶段
approved
商品名
Cholestat;Coledis;Colemin;Corolin;Denan;Labistatin;Lipex;Lodales;Medipo;Nivelipol;Pantok;Rendapid;Simovil;Sinvacor;Sivastin;Synvinolin;Vasotenal;Zocor;Zocord;
同义名
Simvastatin [Usan:Ban:Inn];Simvastatina [Spanish];Simvastatine [French];Simvastatinum [Latin];
基本介绍

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]

生产厂家
  • Accord healthcare inc
  • Aurobindo pharma ltd
  • Dr reddys laboratories inc
  • Dr reddys laboratories ltd
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lupin ltd
  • Matrix laboratories ltd
  • Merck research laboratories div merck co inc
  • Perrigo r and d co
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Synthon pharmaceuticals ltd
  • Watson laboratories inc
  • Zydus pharmaceuticals usa inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE: Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med. 2007 Jul 19;5:20. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes Not Available
Substructures Not Available
适应症
hyperlipidemi 高血脂;
药理
Indication 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.
Pharmacodynamics 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.
Mechanism of action 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.
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

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Simvastatin
simvastatin hydroxy acid Details
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
Clearance Not Available
Toxicity The most common adverse reactions that lead to discontinuation of therapy include gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%).
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 135-138 °C PhysProp
water solubility Insoluble FDA label
logP 4.68 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 1.22e-02 g/l ALOGPS
logP 4.51 ALOGPS
logP 4.46 ChemAxon
logS -4.5 ALOGPS
pKa (strongest acidic) 14.91 ChemAxon
pKa (strongest basic) -2.8 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 72.83 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 117.68 ChemAxon
polarizability 47.85 ChemAxon
药物相互作用
Drug Interaction
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.
Rifampin 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.
食物相互作用
  • Avoid alcohol.
  • Avoid drastic changes in dietary habit.
  • Avoid taking with grapefruit juice.

返回 | 收藏