Tìm theo
Atorvastatin
Các tên gọi khác (1) :
  • Lipovastatinklonal
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 134523-00-5
ATC: C10AA05
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C33H34FN2O5
PTK: 557.6319
Atorvastatin (Lipitor) is a member of the drug class known as statins. It is used for lowering cholesterol. Atorvastatin is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in cholesterol biosynthesis via the mevalonate pathway. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate. Atorvastatin acts primarily in the liver. Decreased hepatic cholesterol levels increases hepatic uptake of cholesterol and reduces plasma cholesterol levels.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C33H34FN2O5
Phân tử khối
557.6319
Monoisotopic mass
557.245175413
InChI
InChI=1/C33H35FN2O5/c1-21(2)31-30(33(41)35-25-11-7-4-8-12-25)29(22-9-5-3-6-10-22)32(23-13-15-24(34)16-14-23)36(31)18-17-26(37)19-27(38)20-28(39)40/h3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40)/p-1
InChI Key
InChIKey=XUKUURHRXDUEBC-UHFFFAOYNA-M
IUPAC Name
7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate
Traditional IUPAC Name
7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrol-1-yl]-3,5-dihydroxyheptanoate
SMILES
CC(C)C1=C(C(=O)NC2=CC=CC=C2)C(=C(N1CCC(O)CC(O)CC([O-])=O)C1=CC=C(F)C=C1)C1=CC=CC=C1
Độ tan chảy
159.2-160.7 °C
Độ hòa tan
Sodium salt soluble in water, 20.4 ug/mL (pH 2.1), 1.23 mg/mL (pH 6.0)
logP
5.7
logS
-6.1
pKa (strongest acidic)
4.33
pKa (Strongest Basic)
-2.7
PSA
114.62 Å2
Refractivity
169.04 m3·mol-1
Polarizability
59.7 Å3
Rotatable Bond Count
12
H Bond Acceptor Count
5
H Bond Donor Count
3
Physiological Charge
-1
Number of Rings
4
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Atorvastatin, a selective, competitive HMG-CoA reductase inhibitor, is used to lower serum total and LDL cholesterol, apoB, and triglyceride levels while increasing HDL cholesterol. 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, atorvastatin reduces the risk of cardiovascular morbidity and mortality. Atorvastatin has a unique structure, long half-life, and hepatic selectivity, explaining its greater LDL-lowering potency compared to other HMG-CoA reductase inhibitors.
Cơ Chế Tác Dụng : Atorvastatin (Lipitor) is a member of the drug class known as statins. It is used for lowering cholesterol. Atorvastatin is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in cholesterol biosynthesis via the mevalonate pathway. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate. Atorvastatin acts primarily in the liver. Decreased hepatic cholesterol levels increases hepatic uptake of cholesterol and reduces plasma cholesterol levels. Atorvastatin selectively and competitively inhibits the hepatic enzyme HMG-CoA reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate in the cholesterol biosynthesis pathway, this results in a subsequent decrease in hepatic cholesterol levels. Decreased hepatic cholesterol levels stimulates upregulation of hepatic LDL-C receptors which increases hepatic uptake of LDL-C and reduces serum LDL-C concentrations.
Dược Động Học :
▧ Absorption :
Atorvastatin is rapidly absorbed after oral administration with maximum plasma concentrations achieved in 1 to 2 hours. The absolute bioavailability of atorvastatin (parent drug) is approximately 14% and the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%. The low systemic bioavailability is due to presystemic clearance by gastrointestinal mucosa and first-pass metabolism in the liver.
▧ Volume of Distribution :
381 L
▧ Protein binding :
>98% bound to plasma proteins
▧ Metabolism :
Atorvastatin is extensively metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation products. In vitro inhibition of HMG-CoA reductase by ortho- and parahydroxylated metabolites is equivalent to that of atorvastatin. Approximately 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites. CYP3A4 is also involved in the metabolism of atorvastatin.
▧ Route of Elimination :
Eliminated primarily in bile after hepatic and/or extrahepatic metabolism. Does not appear to undergo significant enterohepatic recirculation. Less than 2% of the orally administered dose is recovered in urine.
▧ Half Life :
14 hours, but half-life of HMG-CoA inhibitor activity is 20-30 hours due to longer-lived active metabolites
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.
Chỉ Định : May be used as primary prevention in individuals with multiple risk factors for coronary heart disease (CHD) and as secondary prevention in individuals with CHD to reduce the risk of myocardial infarction (MI), stroke, angina, and revascularization procedures. May be used to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). May be used in the treatment of primary hypercholesterolemia and mixed dyslipidemia, homozygous familial hypercholesterolemia, primary dysbetalipoproteinemia, and/or hypertriglyeridemia as an adjunct to dietary therapy to decrease serum total and low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and triglyceride concentrations, while increasing high-density lipoprotein cholesterol (HDL-C) levels.
Tương Tác Thuốc :
  • Aliskiren Therapy modification should be considered because atorvastatin increases aliskiren serum concentration.
  • Alvimopan Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
  • Amprenavir Amprenavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
  • Atazanavir Atazanavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
  • Bezafibrate Increased risk of myopathy/rhabdomyolysis
  • Boceprevir Boceprevir increases the exposure of atorvastatin. Concomitant therapy should be closely monitored.
  • Bosentan Bosentan may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if bosentan is initiated, discontinued or dose changed.
  • Carbamazepine Carbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of atorvastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if carbamazepine is initiated, discontinued or dose changed.
  • Clarithromycin The macrolide, clarithromycin, may increase the toxicity of the statin, atorvastatin.
  • Colchicine Increased risk of rhadbomyolysis with this combination.
  • Cyclosporine Possible myopathy and rhabdomyolysis
  • Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if delavirdine is initiated, discontinued or dose changed.
  • Diltiazem Diltiazem may increase the serum concentration of atorvastatin. Atorvastatin 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 atorvastatin. Lower doses of atorvastatin or consider rosuvastatin as cholesterol lowering therapy as there is no significant interaction between rosuvastatin and dronedarone.
  • Efavirenz Efavirenz may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if efavirenz is initiated, discontinued or dose changed.
  • Eltrombopag Eltrombopag increases levels of Atorvastatin via metabolism decrease.
  • Erythromycin The macrolide, erythromycin, may increase the toxicity of the statin, atorvastatin.
  • Etravirine Atorvastatin, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to monitor continued efficacy of atorvastatin 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 atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin 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 atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if imatinib is initiated, discontinued or dose changed.
  • Indinavir Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
  • Itraconazole Increased risk of myopathy/rhabdomyolysis
  • Josamycin The macrolide, josamycin, may increase the toxicity of the statin, atorvastatin.
  • Ketoconazole Increased risk of myopathy/rhabdomyolysis
  • Liraglutide These agents may have decreased C max and a delayed T max during coadministration.
  • Lomitapide Atorvastatin, and other weak CYP3A4 inhibitors (such as amiodarone, amlodipine, alprazolam, bicalutamide, cilostazol, cimetidine, cyclosporine, fluoxetine, fluvoxamine, ginko, goldenseal, isoniazide, lapatinib, nilotinib, oral contraceptives, pazopanib, ranitidine, ranolazine, tipranavir/ritonavir, ticagrelor, zileuton) increase lomitapide levels by 2-fold. Thus lomipatide should be dosed at a maximum of 30mg daily when used concomitantly with weak inhibitors of CYP3A4.
  • Nefazodone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nefazodone is initiated, discontinued or dose changed.
  • Nelfinavir Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nelfinavir is initiated, discontinued or dose changed.
  • Nevirapine Nevirapine, a strong CYP3A4 inducer, may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nevirapine is initiated, discontinued or dose changed.
  • Quinupristin This combination presents an increased risk of toxicity
  • Rifabutin Rifabutin may decrease the effect of atorvastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atorvastatin if rifabutin is initiated, discontinued or dose changed.
  • Rifampicin Rifampin may decrease the effect of atorvastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atorvastatin if rifampin is initiated, discontinued or dose changed.
  • Ritonavir Ritonavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if ritonavir is initiated, discontinued or dose changed.
  • Saquinavir Saquinavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if saquinavir is initiated, discontinued or dose changed.
  • Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
  • Telithromycin The macrolide antibiotic, telithromycin, may increase the serum concentration of atorvastatin by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atorvastatin if telithromycin is initiated, discontinued or dose changed.
  • Tipranavir Tipranavir, co-administered with Ritonavir, increases the adverse/toxic effects of Atorvastatin. Concomitant therapy should be avoided.
  • Topotecan The p-glycoprotein inhibitor, Atorvastatin, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
  • Verapamil Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Atorvastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce lovastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Atorvastatin if Verapamil is initiated, discontinued or dose changed.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Tablet - Oral - 10 mg
Tablet - Oral - 20 mg
Tablet - Oral - 40 mg
Tablet - Oral - 80 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Lipitor 10 mg Tablet
    Giá bán buôn : USD >1.87
    Đơn vị tính : tablet
  • Biệt dược thương mại : Lipitor 20 mg Tablet
    Giá bán buôn : USD >2.34
    Đơn vị tính : tablet
  • Biệt dược thương mại : Lipitor 40 mg Tablet
    Giá bán buôn : USD >2.52
    Đơn vị tính : tablet
  • Biệt dược thương mại : Lipitor 80 mg Tablet
    Giá bán buôn : USD >2.52
    Đơn vị tính : tablet
  • Biệt dược thương mại : Lipitor 10 mg tablet
    Giá bán buôn : USD >3.5
    Đơn vị tính : tablet
  • Biệt dược thương mại : Lipitor 20 mg tablet
    Giá bán buôn : USD >5.0
    Đơn vị tính : tablet
  • Biệt dược thương mại : Lipitor 40 mg tablet
    Giá bán buôn : USD >5.0
    Đơn vị tính : tablet
  • Biệt dược thương mại : Lipitor 80 mg tablet
    Giá bán buôn : USD >5.0
    Đơn vị tính : tablet
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01076
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C06834
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D07474
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=22164
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0071-0155-23
PharmGKB
http://www.pharmgkb.org/drug/PA448500
Wikipedia
http://en.wikipedia.org/wiki/Atorvastatin
RxList
http://www.rxlist.com/cgi/generic/atorvastatin.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/lip1230.shtml
Drugs.com
http://www.drugs.com/atorvastatin.html
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