Tìm theo
Ranolazine
Các tên gọi khác (1) :
  • Ranexa
Thuốc Gốc
Small Molecule
CAS: 142387-99-3
ATC: C01EB18
ĐG : Atlantic Biologicals Corporation , http://www.atlanticbiologicals.com
CTHH: C24H33N3O4
PTK: 427.5365
Ranolazine is an antianginal medication. On January 31, 2006, ranolazine was approved for use in the United States by the FDA for the treatment of chronic angina. [Wikipedia]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C24H33N3O4
Phân tử khối
427.5365
Monoisotopic mass
427.247106559
InChI
InChI=1S/C24H33N3O4/c1-18-7-6-8-19(2)24(18)25-23(29)16-27-13-11-26(12-14-27)15-20(28)17-31-22-10-5-4-9-21(22)30-3/h4-10,20,28H,11-17H2,1-3H3,(H,25,29)
InChI Key
InChIKey=XKLMZUWKNUAPSZ-UHFFFAOYSA-N
IUPAC Name
N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide
Traditional IUPAC Name
ranolazine
SMILES
COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC2=C(C)C=CC=C2C)CC1
Độ hòa tan
Very slightly soluble
logP
1.6
logS
-3.6
pKa (strongest acidic)
13.6
pKa (Strongest Basic)
7.17
PSA
74.27 Å2
Refractivity
123.46 m3·mol-1
Polarizability
47.22 Å3
Rotatable Bond Count
9
H Bond Acceptor Count
6
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : Ranolazine has antianginal and anti-ischemic effects that do not depend upon reductions in heart rate or blood pressure. It is the first new anti-anginal developed in over 20 years.
Cơ Chế Tác Dụng : Ranolazine is an antianginal medication. On January 31, 2006, ranolazine was approved for use in the United States by the FDA for the treatment of chronic angina. [Wikipedia] The mechanism of action of ranolazine is unknown. It does not increase the rate-pressure product, a measure of myocardial work, at maximal exercise. In vitro studies suggest that ranolazine is a P-gp inhibitor. Ranolazine is believed to have its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium level that ranolazine affects the sodium-dependent calcium channels during myocardial ischemia. Thus, ranolazine indirectly prevents the calcium overload that causes cardiac ischemia.
Dược Động Học :
▧ Absorption :
Absorption is highly variable. After oral administration of ranolazine as a solution, 73% of the dose is systemically available as ranolazine or metabolites. The bioavailability of oral ranolazine relative to that from a solution is 76%.
▧ Protein binding :
62%
▧ Metabolism :
Hepatic, metabolized mainly by CYP3A and to a lesser extent by CYP2D6. The pharmacologic activity of the metabolites has not been well characterized.
▧ Route of Elimination :
Ranolazine is metabolized rapidly and extensively in the liver and intestine; less than 5% is excreted unchanged in urine and feces.
▧ Half Life :
7 hours
Độc Tính : In the event of overdose, the expected symptoms would be dizziness, nausea/vomiting, diplopia, paresthesia, and confusion. Syncope with prolonged loss of consciousness may develop.
Chỉ Định : For the treatment of chronic angina. It should be used in combination with amlodipine, beta-blockers or nitrates.
Tương Tác Thuốc :
  • Amiodarone Possible additive effect on QT prolongation
  • Amprenavir Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentratin of ranolazine by inhibiting its metabolism. Concomitant therapy is contraindicated.
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Atazanavir Atazanavir, a strong CYP3A4 inhibitor, may increase the serum level of ranolazine. Concomitant therapy is contraindicated.
  • Bicalutamide CYP3A4 inhibitors like ranolazine may increase the serum concentration of ranolazine. Consider therapy modification.
  • Bretylium Possible additive effect on QT prolongation
  • Clarithromycin Clarithromycin, a strong CYP3A4 inhibitor, may increase the serum level of ranolazine. Concomitant therapy is contraindicated.
  • Clotrimazole CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of ranolazine. Limit the ranolazine dose to a maximum of 500mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Monitor for increased effects/toxicity of ranolazine during concomitant use.
  • Conivaptan CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. The manufacturer contraindicates the use of ranolazine and strong CYP3A4 inhibitors (such as the azole antifungals).1 Monitor for increased effects/toxicity of ranolazine during concomitant use.
  • Digoxin Ranolazine may increase the serum level of digoxin. Monitor for changes in the serum level and therapeutic and adverse effects of digoxin if ranolazine is initiated, discontinued or dose changed.
  • Diltiazem Diltiazem may increase the serum concentration of ranolazine. Consider alternate therapy or limit ranolazine dose to 500 mg twice daily and monitor for changes in the therapeutic and adverse effects if diltiazem is initiated, discontinued or dose changed.
  • Dirithromycin Increased levels of ranolazine - risk of toxicity
  • Disopyramide Possible additive effect on QT prolongation
  • Dofetilide Possible additive effect on QT prolongation
  • Erythromycin Increased levels of ranolazine - risk of toxicity
  • Fluconazole Increased levels of ranolazine - risk of toxicity
  • Fosamprenavir Increased levels of ranolazine - risk of toxicity
  • Ibutilide Possible additive effect on QT prolongation
  • Indinavir Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of ranolazine by decreasing its metabolism. Concomitant therapy is contraindicated.
  • Itraconazole Increased levels of ranolazine - risk of toxicity
  • Ketoconazole Increased levels of ranolazine - risk of toxicity
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Moricizine Possible additive effect on QT prolongation
  • Nelfinavir Increased levels of ranolazine - risk of toxicity
  • Procainamide Possible additive effect on QT prolongation
  • Quinidine Possible additive effect on QT prolongation
  • Ritonavir Increased levels of ranolazine - risk of toxicity
  • Saquinavir Increased levels of ranolazine - risk of toxicity
  • Simvastatin 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.
  • Sotalol Possible additive effect on QT prolongation
  • Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Tamoxifen Ranolazine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
  • Tamsulosin Ranolazine, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Ranolazine is initiated, discontinued, or dose changed.
  • Telithromycin Telithromycin may reduce clearance of Ranolazine. Concomitant therapy should be avoided.
  • Thioridazine Possible additive effect on QT prolongation
  • Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
  • Tipranavir Increased levels of ranolazine - risk of toxicity
  • Tolterodine Ranolazine may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Topotecan The p-glycoprotein inhibitor, Ranolazine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
  • Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
  • Tramadol Ranolazine may decrease the effect of Tramadol by decreasing active metabolite production.
  • Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Verapamil Verapamil, a CYP3A4 inhibitor, may increase the serum concentration of Ranolazine. Concomitant therapy is contraindicated.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of ranolazine by decreasing its metabolism. Additive QTc prolongation may also occur. Concomitant therapy is contraindicated.
  • Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
  • Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
  • Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Liều Lượng & Cách Dùng : Tablet, film coated, extended release - Oral
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Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00243
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=56959
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505145
ChemSpider
http://www.chemspider.com/Chemical-Structure.51354.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/61958-1001-1
PharmGKB
http://www.pharmgkb.org/drug/PA164746007
Wikipedia
http://en.wikipedia.org/wiki/Ranolazine
RxList
http://www.rxlist.com/cgi/generic/ranexa.htm
Drugs.com
http://www.drugs.com/cdi/ranolazine.html
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