药品详细
Fluvastatin (氟伐他汀 )
化学结构式图
中文名
氟伐他汀
英文名
Fluvastatin
分子式
Not Available
化学名
(3S,5R,6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid
分子量
Average: 411.4659
Monoisotopic: 411.184586530
Monoisotopic: 411.184586530
CAS号
93957-54-1
ATC分类
C10A 未知
药物类型
small molecule
阶段
商品名
Canef (AstraZeneca);Cranoc (Astellas);Lescol (Novartis Pharmaceuticals );Lescol XL (Novartis Pharmaceuticals);
同义名
Fluindostatin;Fluvastatin sodium;Fluvastatina [INN-Spanish];Fluvastatine [INN-French];Fluvastatinum [INN-Latin];
基本介绍
Fluvastatin 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. Fluvastatin belongs to a class of medications called statins and is used to reduce plasma cholesterol levels and prevent cardiovascular disease.
生产厂家
- Novartis pharmaceuticals corp
封装厂家
参考
| Synthesis Reference | Not Available |
| General Reference | Not Available |
剂型
| Form | Route | Strength |
|---|---|---|
| Capsule | Oral | 20 mg |
| Capsule | Oral | 40 mg |
| Tablet, extended release | Oral | 80 mg |
规格
| Unit description | Cost | Unit |
|---|---|---|
| Lescol XL 80 mg 24 Hour tablet | 4.25 USD | tablet |
| Lescol xl 80 mg tablet | 4.24 USD | tablet |
| Lescol xl 80 mg tablet sa | 3.66 USD | tablet |
| Lescol 20 mg capsule | 3.38 USD | capsule |
| Lescol 40 mg capsule | 3.37 USD | capsule |
| Lescol Xl 80 mg Extended-Release Tablet | 1.62 USD | tablet |
| Lescol 40 mg Capsule | 1.35 USD | capsule |
| Lescol 20 mg Capsule | 0.96 USD | capsule |
化合物类型
| Type | small molecule |
| Classes |
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| Substructures |
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适应症
hyperlipidemi 高血脂;
药理
| Indication | To be used as an adjunct to dietary therapy to prevent cardiovascular events. May be used as secondary prevention in patients with coronary heart disease (CHD) to reduce the risk of requiring coronary revascularization procedures, for reducing progression of coronary atherosclerosis in hypercholesterolemic patients with CHD, and for the treatment of primary hypercholesterolemia and mixed dyslidipidemia. | |||||||||||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | Fluvastatin, the first synthetically-derived HMG-CoA reductase inhibitor, is a hydrophilic, acidic, antilipemic agent used to lower cholesterol and triglyceride levels associated with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb), to slow the progression of coronary atherosclerosis in patients with CHD and as secondary prevention therapy in patients with CHD to reduce the risk of requiring coronary revascularization procedures. Although similar to lovastatin, simvastatin, and pravastatin, fluvastatin has a shorter half-life, no active metabolites, extensive protein binding, and minimal CSF penetration. Fluvastatin acts primarily in the liver. It is prepared as a racemate of two erythro enantiomers of which the 3R,5S enantiomer exerts the pharmacologic effect. | |||||||||||||||||||||||||||||||||||||||||||||
| Mechanism of action | Fluvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis. Inhibition results in a decrease in hepatic cholesterol levels which stimulates the synthesis of LDL receptors and increases hepatic uptake of LDL cholesterol. The end result is decreased levels of plasma total and LDL cholesterol. | |||||||||||||||||||||||||||||||||||||||||||||
| Absorption | Rapidly and almost completely absorbed (> 90%), but undergoes extensive first pass metabolism. Bioavailability is 24% (range 9-50%). | |||||||||||||||||||||||||||||||||||||||||||||
| Volume of distribution |
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| Protein binding | 98% bound to plasma proteins | |||||||||||||||||||||||||||||||||||||||||||||
| Metabolism |
Undergoes hepatic metabolism primarily via hydroxylation of the indole ring at the 5- and 6-positions to 5-hydroxy fluvastatin and 6-hydroxy fluvastatin, respectively. N-dealkylation to N-desisopropyl fluvastatin and beta-oxidation of the side chain also occurs. Metabolized primarily by the CYP2C9 isozyme system (75%), and to a lesser extent by CYP3A4 (~20%) and CYP2C8 (~5%). Hydroxylated metabolites retain some pharmcological activity, but are present as conjugates (glucuronides and sulfates) in the blood and are rapidly eliminated via bile into feces.
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| Route of elimination | Fluvastatin is metabolized in the liver, primarily via hydroxylation of the indole ring at the 5- and 6-positions. In vitro studies demonstrated that fluvastatin undergoes oxidative metabolism, predominantly via 2C9 isozyme systems (75%). No significant (<6%) renal excretion of fluvastatin occurs in humans. | |||||||||||||||||||||||||||||||||||||||||||||
| Half life | 1-3 hours | |||||||||||||||||||||||||||||||||||||||||||||
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| Toxicity | Generally well-tolerated. May cause GI upset (diarrhea, nausea, constipation, gas, abdominal pain), myotoxicity (mypothy, myositis, rhabdomyolysis), and hepatotoxicity. | |||||||||||||||||||||||||||||||||||||||||||||
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理化性质
| Properties | |||||||||||||||||||||||||||||||||||||
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| State | solid | ||||||||||||||||||||||||||||||||||||
| Melting point | 194-197oC | ||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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药物相互作用
| Drug | Interaction |
|---|---|
| Acenocoumarol | Fluvastatin may increase the anticoagulant effect of acenocoumarol. Monitor for changes in the therapeutic and adverse effects of acenocoumarol if fluvastatin is initiated, discontinued or dose changed. |
| Anisindione | Fluvastatin may increase the anticoagulant effect of anisindione. Monitor for changes in the therapeutic and adverse effects of anisindione if fluvastatin if initiated, discontinued or dose changed. |
| Bezafibrate | Increased risk of myopathy/rhabdomyolysis |
| Cholestyramine | Increased/decreased effect according to spacing |
| Colchicine | Increased risk of rhabdomyolysis with this combination |
| Colestipol | Increased/decreased effect according to spacing |
| Cyclosporine | Possible myopathy and rhabdomyolysis |
| Dicumarol | Fluvastatin may increase the anticoagulant effect of dicumarol. Monitor for changes in the therapeutic and adverse effects of dicumarol if fluvastatin if initiated, discontinued or dose changed. |
| Fenofibrate | Increased risk of myopathy/rhabdomyolysis |
| Fluconazole | Fluconazole may increase the serum concentration of fluvastatin by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of fluvastatin if fluconazole is initiated, discontinued or dose changed. |
| Gemfibrozil | Increased risk of myopathy/rhabdomyolysis |
| Rifabutin | Rifabutin may decrease the effect of fluvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of fluvastatin if rifabutin is initiated, discontinued or dose changed. |
| Rifampin | Rifampin may decrease the effect of fluvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of fluvastatin if rifampin is initiated, discontinued or dose changed. |
| Warfarin | Fluvastatin may increase the anticoagulant effect of warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if fluvastatin is initiated, discontinued or dose changed. |
食物相互作用
- May be taken with or without food, but should be taken consistently.
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