Tìm theo
Fluvastatin
Hormon, Nội tiết tố
Thuốc Gốc
Small Molecule
CAS: 93957-54-1
ATC: C10AA04
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C24H26FNO4
PTK: 411.4659
Fluvastatin is an antilipemic agent that competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase 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. It is also the first entirely synthetic HMG-CoA reductase inhibitor and is structurally distinct from the fungal derivatives of this therapeutic class.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C24H26FNO4
Phân tử khối
411.4659
Monoisotopic mass
411.18458653
InChI
InChI=1/C24H26FNO4/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30)/b12-11+/t18-,19-/s2
InChI Key
InChIKey=FJLGEFLZQAZZCD-NDDZYTDBNA-N
IUPAC Name
(3R,5S,6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid
Traditional IUPAC Name
(3R,5S)-fluvastatin
SMILES
CC(C)N1C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C(C2=CC=CC=C12)C1=CC=C(F)C=C1
Độ tan chảy
194-197 °C
Độ hòa tan
0.46 mg/L
logP
4.5
logS
-5
pKa (strongest acidic)
4.56
pKa (Strongest Basic)
-2.8
PSA
82.69 Å2
Refractivity
114.86 m3·mol-1
Polarizability
43.9 Å3
Rotatable Bond Count
8
H Bond Acceptor Count
4
H Bond Donor Count
3
Physiological Charge
-1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : Fluvastatin is an antilipemic agent that competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase 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. It is also the first entirely synthetic HMG-CoA reductase inhibitor and is structurally distinct from the fungal derivatives of this therapeutic class. 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.
Dược Động Học :
▧ Absorption :
Rapidly and almost completely absorbed (> 90%), but undergoes extensive first pass metabolism. Bioavailability is 24% (range 9-50%) when a 10 mg dose is given. The mean relative bioavailability of the extended-release tablet is 29% (range: 9% to 66%) compared to an immediate-release capsule administered under fasting conditions. When given orally, fluvastatin reaches peak concentrations (Tmax) in less than one hour. Taking the extended release tablet with a high-fat meal will delay absorption (Tmax = 6 hours) and increase bioavailability by approximately 50%. However, the maximum concentration of fluvastatin sodium extended-release tablets seen after a high fat meal is less than the peak concentration following a single dose or twice daily dose of the 40 mg fluvastatin capsule.
▧ Volume of Distribution :
* 0.35 L/kg
▧ Protein binding :
98% bound to plasma proteins. At therapeutic concentrations, the protein binding of fluvastatin is not affected by warfarin, salicylic acid and glyburide.
▧ 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. Both enantiomers of fluvastatin are metabolized in a similar manner. Fluvastatin also undergoes glucuronidation via UGT enzymes.
▧ Route of Elimination :
When orally administered, fluvastatin is primarily excreted in the faces ( ~90%) as metabolites, with less than 2% present as unchanged drug. Approximately 5% was recovered in the urine.
▧ Half Life :
3 hours
▧ Clearance :
* 0.8 L/h/kg * 107 ± 38.1 L/h [Hypercholesterolemia patients receiving a single dose of 20 mg] * 87.8 ± 45 L/h [Hypercholesterolemia patients receiving 20 mg twice daily] * 108 ± 44.7 L/h [Hypercholesterolemia patients receiving 40 mg single] * 64.2 ± 21.1 L/h [Hypercholesterolemia patients receiving 40 mg twice daily]
Độc Tính : Generally well-tolerated. May cause gastrointestinal upset (diarrhea, nausea, constipation, gas, abdominal pain), myotoxicity (mypothy, myositis, rhabdomyolysis), and hepatotoxicity.
Chỉ Định : 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.
Tương Tác Thuốc :
  • 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
  • Dicoumarol 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.
  • Eltrombopag Increases levels of Fluvastatin via metabolism decrease. OATP transporter protein inhibition.
  • Etravirine Fluvastatin, when administered concomitantly with etravirin, may experience an increase in serum concentration. It is recommended to monitor for signs of toxicity from fluvastatin, such as myopathy and hepatic enzyme elevations.
  • 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
  • Repaglinide Inhibitors of CYP3A4 and P-glycoprotein may increase serum concentrations of repaglinide. Monitor concomitant therapy closely.
  • 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.
  • Rifampicin 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.
Liều Lượng & Cách Dùng : Capsule - Oral - 20 mg, 40 mg
Tablet, extended release - Oral - 80 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01095
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07014
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D07983
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0078-0176-05
PharmGKB
http://www.pharmgkb.org/drug/PA449688
Wikipedia
http://en.wikipedia.org/wiki/Fluvastatin
RxList
http://www.rxlist.com/cgi/generic2/fluvastatinxl.htm
Drugs.com
http://www.drugs.com/cdi/fluvastatin.html
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