Tìm theo
Lovastatin
Các tên gọi khác (13 ) :
  • (1S,3R,7S,8S,8AR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(2R,4R)-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl (S)-2-methyl-butyrate
  • 2beta,6alpha-Dimethyl-8alpha-(2-methyl-1-oxobutoxy)-mevinic acid lactone
  • 6-alpha-methylcompactin
  • 6alpha-Methylcompactin
  • 6α-methylcompactin
  • LOVASTATIN
  • Lovastatina
  • Lovastatine
  • Lovastatinum
  • Mevacor
  • Mevinolin
  • MK-803
  • ML-530b
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 75330-75-5
ATC: C10AA02
ĐG : Actavis Group , http://www.actavis.com
CTHH: C24H36O5
PTK: 404.5396
Lovastatin is a cholesterol-lowering agent that belongs to the class of medications called statins. It was the second agent of this class discovered. It was discovered by Alfred Alberts and his team at Merck in 1978 after screening only 18 compounds over 2 weeks. The agent, also known as mevinolin, was isolated from the fungi Aspergillus terreus. Research on this compound was suddenly shut down in 1980 and the drug was not approved until 1987. Interesting, Akira Endo at Sankyo Co. (Japan) patented lovastatin isolated from Monascus ruber four months before Merck. Lovastatin was found to be 2 times more potent than its predecessor, mevastatin, the first discovered statin. Like mevastatin, lovastatin is structurally similar to hydroxymethylglutarate (HMG), a substituent of HMG-Coenzyme A (HMG-CoA), a substrate of the cholesterol biosynthesis pathway via the mevalonic acid pathway. Lovastatin is a competitive inhibitor of HMG-CoA reductase with a binding affinity 20,000 times greater than HMG-CoA. Lovastatin differs structurally from mevastatin by a single methyl group at the 6’ position. Lovastatin is a prodrug that is activated by in vivo hydrolysis of the lactone ring. It, along with mevastatin, has served as one of the lead compounds for the development of the synthetic compounds used today.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C24H36O5
Phân tử khối
404.5396
Monoisotopic mass
404.256274262
InChI
InChI=1S/C24H36O5/c1-5-15(3)24(27)29-21-11-14(2)10-17-7-6-16(4)20(23(17)21)9-8-19-12-18(25)13-22(26)28-19/h6-7,10,14-16,18-21,23,25H,5,8-9,11-13H2,1-4H3/t14-,15-,16-,18+,19+,20-,21-,23-/m0/s1
InChI Key
InChIKey=PCZOHLXUXFIOCF-BXMDZJJMSA-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 (2S)-2-methylbutanoate
Traditional IUPAC Name
lovastatin
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@@H](C)CC
Độ tan chảy
174.5 °C
Độ hòa tan
0.0004 mg/mL
logP
4.26
logS
-4.2
pKa (strongest acidic)
14.91
pKa (Strongest Basic)
-2.8
PSA
72.83 Å2
Refractivity
113.18 m3·mol-1
Polarizability
46.11 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 : The primary cause of cardiovascular disease is atherosclerotic plaque formation. Sustained elevations of cholesterol in the blood increase the risk of cardiovascular disease. Lovastatin lowers hepatic cholesterol synthesis by competitively inhibiting HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in the cholesterol biosynthesis pathway via the mevalonic acid pathway. Decreased hepatic cholesterol levels causes increased uptake of low density lipoprotein (LDL) cholesterol and reduces cholesterol levels in the circulation. At therapeutic doses, lovastatin decreases serum LDL cholesterol by 29-32%, increases high density lipoprotein (HDL) cholesterol by 4.6-7.3%, and decrease triglyceride levels by 2-12%. HDL cholesterol is thought to confer protective effects against CV disease, whereas high LDL and triglyceride levels are associated with higher risk of disease.
Cơ Chế Tác Dụng : Lovastatin is a cholesterol-lowering agent that belongs to the class of medications called statins. It was the second agent of this class discovered. It was discovered by Alfred Alberts and his team at Merck in 1978 after screening only 18 compounds over 2 weeks. The agent, also known as mevinolin, was isolated from the fungi Aspergillus terreus. Research on this compound was suddenly shut down in 1980 and the drug was not approved until 1987. Interesting, Akira Endo at Sankyo Co. (Japan) patented lovastatin isolated from Monascus ruber four months before Merck. Lovastatin was found to be 2 times more potent than its predecessor, mevastatin, the first discovered statin. Like mevastatin, lovastatin is structurally similar to hydroxymethylglutarate (HMG), a substituent of HMG-Coenzyme A (HMG-CoA), a substrate of the cholesterol biosynthesis pathway via the mevalonic acid pathway. Lovastatin is a competitive inhibitor of HMG-CoA reductase with a binding affinity 20,000 times greater than HMG-CoA. Lovastatin differs structurally from mevastatin by a single methyl group at the 6’ position. Lovastatin is a prodrug that is activated by in vivo hydrolysis of the lactone ring. It, along with mevastatin, has served as one of the lead compounds for the development of the synthetic compounds used today. Lovastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Lovastatin is a prodrug that is activated in vivo via hydrolysis of the lactone ring to form the β-hydroxyacid. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind to HMG-CoA reductase with 20,000 times greater affinity than its natural substrate. The bicyclic portion of lovastatin binds to the coenzyme A portion of the active site.
Dược Động Học :
▧ Absorption :
Studies suggest that <5% of the oral dose reaches the general circulation as active inhibitors. Time to peak serum concentration is 2-4 hours. Lovastatin undergoes extensive first-pass metabolism so the availability of the drug in the system is low and variable.
▧ Volume of Distribution :
Lovastatin is able to cross the blood-brain-barrier and placenta.
▧ Protein binding :
Lovastatin and its β-hydroxyacid metabolites are highly protein bound (>95%).
▧ Metabolism :
Lovastatin is hepatically metabolized in which the major active metabolites are the β-hydroxyacid of lovastatin, the 6’-hydroxy derivative, and two additional metabolites.
▧ Route of Elimination :
Lovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. 83% of the orally administered dose is excreted in bile and 10% is excreted in urine.
▧ Half Life :
5.3 hours
Độc Tính : LD50>1000 mg/kg (orally in mice)
Chỉ Định : For management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia. For primary prevention of coronary heart disease and to slow progression of coronary atherosclerosis in patients with coronary heart disease.
Tương Tác Thuốc :
  • Acenocoumarol Lovastatin may increase the anticoagulant effect of acenocoumarol. Monitor for changes in the therapeutic and adverse effects of acenocoumarol if lovastatin is initiated, discontinued or dose changed.
  • Amprenavir Amprenavir may increase the serum concentration of the lovastatin. Concomitant therapy is contraindicated.
  • Anisindione Lovastatin may increase the anticoagulant effect of anisindione. Monitor for changes in the therapeutic and adverse effects of anisindione if lovastatin if initiated, discontinued or dose changed.
  • Atazanavir Atazanavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
  • Azithromycin The macrolide antibiotic, azithromycin, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if azithromycin is initiated, discontinued or dose changed.
  • Bezafibrate Increased risk of myopathy/rhabdomyolysis
  • Bosentan Bosentan may decrease the serum concentration of lovastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if bosentan is initiated, discontinued or dose changed.
  • Carbamazepine Carbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of lovastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if carbamazepine is initiated, discontinued or dose changed.
  • Clarithromycin The macrolide, clarithromycin, may increase the toxicity of the statin, lovastatin.
  • Colchicine Increased risk of rhabdomyolysis with this combination
  • Cyclosporine Possible myopathy and rhabdomyolysis
  • Danazol Risk of severe myopathy/rhabdomyolysis with this combination
  • Darunavir Darunavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
  • Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if delavirdine is initiated, discontinued or dose changed.
  • Dicoumarol Lovastatin may increase the anticoagulant effect dicumarol. Monitor for changes in the therapeutic and adverse effects of dicumarol if lovastatin is initiated, discontinued or dose changed.
  • Diltiazem Diltiazem may increase the serum concentration of lovastatin. Lovastatin 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.
  • Efavirenz Efavirenz may decrease the serum concentration of lovastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if efavirenz is initiated, discontinued or dose changed.
  • Erythromycin The macrolide, erythromycin, may increase the toxicity of the statin, lovastatin.
  • Etravirine Lovastatin, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to monitor continued efficacy of lovastatin therapy.
  • Fenofibrate Increased risk of myopathy/rhabdomyolysis
  • Fluconazole Increased risk of myopathy/rhabdomyolysis
  • Fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may increase the effect and toxicity of lovastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
  • Gemfibrozil Increased risk of myopathy/rhabdomyolysis
  • Imatinib Imatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if imatinib is initiated, discontinued or dose changed.
  • Indinavir Indinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
  • Itraconazole Increased risk of myopathy/rhabdomyolysis
  • Josamycin The macrolide, josamycin, may increase the toxicity of the statin, lovastatin.
  • Ketoconazole Increased risk of myopathy/rhabdomyolysis
  • Lomitapide Lovastatin plasma concentrations may increase by lomitapide.
  • Nefazodone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if nefazodone is initiated, discontinued or dose changed.
  • Nelfinavir Nelfinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
  • Nevirapine The strong CYP3A4 inducer, nevirapine, may decrase the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if nevirapine is initiated, discontinued or dose changed.
  • Niacin Risk of severe myopathy/rhabdomyolysis with this combination
  • Quinupristin This combination presents an increased risk of toxicity
  • Rifabutin Rifabutin may decrease the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if rifabutin is initiated, discontinued or dose changed.
  • Rifampicin Rifampin may decrease the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if rifampin is initiated, discontinued or dose changed.
  • Ritonavir Ritonavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
  • Saquinavir Saquinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
  • Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
  • Telithromycin Telithromycin may increase the adverse effects of lovastatin by decreasing its metabolism. Concomitant therapy should be avoided.
  • Ticagrelor Patients receiving more than 40 mg per day of lovastatin may be at increased risk of statin-related adverse effects.
  • Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Lovastatin. Concomitant therapy is contraindicated.
  • Verapamil Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Lovastatin 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 Lovastatin if Verapamil is initiated, discontinued or dose changed.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if voriconazole is initiated, discontinued or dose changed.
  • Warfarin Lovastatin may increase the anticoagulant effect warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if lovastatin is initiated, discontinued or dose changed .
Liều Lượng & Cách Dùng : Tablet - Oral - 10 mg
Tablet - Oral - 20 mg
Tablet - Oral - 40 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Altocor
  • Công ty :
    Sản phẩm biệt dược : Altoprev
  • Công ty : Merck
    Sản phẩm biệt dược : Mevacor
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00227
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=53232
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508223
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07074
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00359
ChemSpider
http://www.chemspider.com/Chemical-Structure.48085.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0378-6510-91
PharmGKB
http://www.pharmgkb.org/drug/PA450272
Wikipedia
http://en.wikipedia.org/wiki/Lovastatin
RxList
http://www.rxlist.com/cgi/generic3/altocor.htm
Drugs.com
http://www.drugs.com/cdi/lovastatin.html
... loading
... loading