药品详细

Ranolazine(雷诺嗪)

基本信息
剂型规格
适应症
药理
临床
理化性质
相互作用
文档
专利
Pathway
文献
序列

化学结构式图

中文名

雷诺嗪

英文名

Ranolazine

分子式

C₂₄H₃₃N₃O₄

化学名

N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide

分子量

Average: 427.5365
Monoisotopic: 427.247106559

CAS号

142387-99-3

ATC分类

C01E 未知

药物类型

small molecule

阶段

approved

商品名

同义名

基本介绍

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]

生产厂家

Gilead sciences inc

封装厂家

参考

Synthesis Reference

Not Available

General Reference

Hale SL, Kloner RA: Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit. J Cardiovasc Pharmacol Ther. 2006 Dec;11(4):249-55. Pubmed
Fraser H, Belardinelli L, Wang L, Light PE, McVeigh JJ, Clanachan AS: Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol. 2006 Dec;41(6):1031-8. Epub 2006 Oct 5. Pubmed
Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L: Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006 Aug 1;48(3):566-75. Epub 2006 Jun 15. Pubmed
Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, Wang W, Skettino SL, Wolff AA: Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA. 2004 Jan 21;291(3):309-16. Pubmed
Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff AA, Skene A, McCabe CH, Braunwald E: Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007 Apr 25;297(16):1775-83. Pubmed

剂型

规格

化合物类型

Type	small molecule

Classes

Acetanilides

Substructures

Hydroxy Compounds
Phenols and Derivatives
Amino Ketones
Piperazines
Ethers
Benzene and Derivatives
Acetanilides
Carboxylic Acids and Derivatives
Aliphatic and Aryl Amines
Catechols
Heterocyclic compounds
Aromatic compounds
Anisoles
Carboxamides and Derivatives
Alcohols and Polyols
Phenyl Esters
Anilines

适应症

药理

Indication	For the treatment of chronic angina. It should be used in combination with amlodipine, beta-blockers or nitrates.
Pharmacodynamics	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.
Mechanism of action	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.
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%.
Volume of distribution	Not Available
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
Clearance	Not Available
Toxicity	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.
Affected organisms	Humans and other mammals
Pathways	Not Available

理化性质

Properties

State

solid

Experimental Properties

Property	Value	Source
water solubility	Very slightly soluble	Not Available
logP	1.6	Not Available

Predicted Properties

Property	Value	Source
water solubility	1.10e-01 g/l	ALOGPS
logP	2.08	ALOGPS
logP	2.83	ChemAxon
logS	-3.6	ALOGPS
pKa (strongest acidic)	13.6	ChemAxon
pKa (strongest basic)	7.17	ChemAxon
physiological charge	1	ChemAxon
hydrogen acceptor count	6	ChemAxon
hydrogen donor count	2	ChemAxon
polar surface area	74.27	ChemAxon
rotatable bond count	9	ChemAxon
refractivity	123.46	ChemAxon
polarizability	47.22	ChemAxon

药物相互作用

Drug	Interaction
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).

食物相互作用

Grapefruit and grapefruit juice should be avoided throughout treatment.
Take without regard to meals.

返回 | 收藏