用户名： 密   码：
注册 | 忘记密码？
药品详细

Propafenone(普罗帕酮)

化学结构式图
中文名
普罗帕酮
英文名
Propafenone
分子式
C21H27NO3
化学名
1-{2-[2-hydroxy-3-(propylamino)propoxy]phenyl}-3-phenylpropan-1-one
分子量
Average: 341.444
Monoisotopic: 341.199093735
CAS号
54063-53-5
ATC分类
C01B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. [PubChem]

生产厂家
  • Glaxosmithkline llc
  • Kv pharmaceutical co
  • Mutual pharmaceutical co inc
  • Pliva inc
  • Vintage pharmaceuticals inc
  • Watson laboratories
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenols and Derivatives
  • Ethers
  • Anisoles
  • Benzoyl Derivatives
  • Acetophenones and Derivatives
Substructures
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Amino Alcohols
  • Aromatic compounds
  • Anisoles
  • Benzoyl Derivatives
  • Alcohols and Polyols
  • Acetophenones and Derivatives
  • Phenyl Esters
  • Ketones
适应症
药理
Indication Used to prolong the time to recurrence of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms in patients without structural heart disease. Also used for the treatment of life-threatening documented ventricular arrhythmias, such as sustained ventricular tachycardia.
Pharmacodynamics Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects, and a direct stabilizing action on myocardial membranes. It is used in the treatment of atrial and ventricular arrhythmias. It works by slowing the influx of sodium ions into the cardiac muscle cells, causing a decrease in excitablity of the cells. Propafenone has local anesthetic activity approximately equal to procaine.
Mechanism of action The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential. In Purkinje fibers, and to a lesser extent myocardial fibers, propafenone reduces the fast inward current carried by sodium ions, which is responsible for the drugs antiarrhythmic actions. Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. At very high concentrations in vitro, propafenone can inhibit the slow inward current carried by calcium but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy.
Absorption Nearly completely absorbed following oral administration (90%). Systemic bioavailability ranges from 5 to 50%, due to significant first-pass metabolism. This wide range in systemic bioavailability is related to two factors: presence of food (food increases bioavailability) and dosage (bioavailability is 3.4% for a 150-mg tablet compared to 10.6% for a 300-mg tablet).
Volume of distribution
  • 252 L
Protein binding 97%
Metabolism
Metabolized primarily in the liver where it is rapidly and extensively metabolized to two active metabolites, 5-hydroxypropafenone and N-depropylpropafenone. These metabolites have antiarrhythmic activity comparable to propafenone but are present in concentrations less than 25% of propafenone concentrations.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Propafenone
N-desalkylpropafenone Details
Propafenone
5-hydroxypropafenone Details
Propafenone
    		N-depropylpropafenone Details
    Route of elimination Approximately 50% of propafenone metabolites are excreted in the urine following administration of immediate release tablets.
    Half life 2-10 hours
    Clearance Not Available
    Toxicity Symptoms of propafenone overdose (usually most severe within the first 3 hours) may include convulsions (rarely), heartbeat irregularities, low blood pressure, and sleepiness.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    water solubility Slightly soluble Not Available
    logP 3.2 Not Available
    Predicted Properties
    Property Value Source
    water solubility 7.58e-03 g/l ALOGPS
    logP 3.1 ALOGPS
    logP 3.54 ChemAxon
    logS -4.7 ALOGPS
    pKa (strongest acidic) 14.09 ChemAxon
    pKa (strongest basic) 9.63 ChemAxon
    physiological charge 1 ChemAxon
    hydrogen acceptor count 4 ChemAxon
    hydrogen donor count 2 ChemAxon
    polar surface area 58.56 ChemAxon
    rotatable bond count 11 ChemAxon
    refractivity 100.21 ChemAxon
    polarizability 39.75 ChemAxon
    药物相互作用
    Drug Interaction
    Acenocoumarol Propafenone may increase the anticoagulant effect of acenocoumarol.
    Aminophylline Propafenone increases the effect of theophylline
    Anisindione Propafenone may increase the anticoagulant effect of anisindione.
    Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
    Cisapride Increased risk of cardiotoxicity and arrhythmias
    Cyclosporine Propafenone increases the effect and toxicity of cyclosporine
    Dicumarol Propafenone may increase the anticoagulant effect of dicumarol.
    Digoxin Propafenone increases the effect of digoxin
    Dihydroquinidine barbiturate Quinidine increases the effect of propafenone
    Duloxetine Possible increase in the levels of this agent when used with duloxetine
    Dyphylline Propafenone increases the effect of theophylline
    Etravirine Propafenone, when used concomitantly with Etravirine, may experience a decrease in serum concentration. It is recommended to monitor for continued efficacy of propafenone therapy.
    Fluoxetine Additive QTc-prolongation may occur increasing the risk of serious life-threatening arrhythmias. Fluoxetine may also increase the serum concentration of propafenone. Use caution during concomitant therapy and monitor for QTc-prolongation.
    Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
    Mesoridazine Increased risk of cardiotoxicity and arrhythmias.
    Metoprolol Propafenone may increase the effect of beta-blocker, metoprolol.
    Mexiletine Propafenone may increase the effect and toxicity of mexilitine.
    Mirabegron Mirabegron is a moderate CYP2D6 inhibitor and may cause an increase in exposure of CYP2D6 substrates. Monitor concomitant therapy closely.
    Oxtriphylline Propafenone increases the effect of theophylline
    Paroxetine Paroxetine may increase the effect and toxicity of propafenone.
    Propranolol Propafenone may increase the effect of the beta-blocker, propranolol.
    Quinidine Quinidine increases the effect of propafenone
    Quinidine barbiturate Quinidine increases the effect of propafenone
    Rifabutin Rifampin decreases the effect of propafenone
    Rifampin Rifampin decreases the effect of propafenone
    Ritonavir Ritonavir increases the effect and toxicity of propafenone
    Sertraline Fluoxetine increases the effect and toxicity of propafenone
    Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
    Terbinafine Terbinafine may reduce the metabolism and clearance of Propafenone. Consider alternate therapy or monitor for therapeutic/adverse effects of Propafenone if Terbinafine is initiated, discontinued or dose changed.
    Terfenadine Increased risk of cardiotoxicity and arrhythmias.
    Theophylline Propafenone increases the effect of theophylline
    Thiopental Thiopental may increase the metabolism and clearance of Propafenone. Monitor for decreased therapeutic effect of Propafenone if Thiopental is initiated.
    Thioridazine Increased risk of cardiotoxicity and arrhythmias.
    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 Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Propafenone. Concomitant therapy is contraindicated.
    Tizanidine Propafenone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
    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.
    Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
    Venlafaxine Propafenone increases the effect and toxicity of venlafaxine
    Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
    Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
    Warfarin Propafenone may increase the anticoagulant effect of warfarin.
    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
    • Always take at the same time in regard to meals.
    • Grapefruit and grapefruit juice should be avoided throughout treatment. Grapefruit can increase serum levels of this product.

    返回 | 收藏