Tìm theo
Dofetilide
Các tên gọi khác (5 ) :
  • beta-((P-Methanesulfonamidophenethyl)methylamino)methanesulfono-P-phenetidide
  • Dofetilida
  • Dofetilide
  • Dofetilidum
  • Tikosyn
Thuốc chống loạn nhịp
Thuốc Gốc
Small Molecule
CAS: 115256-11-6
ATC: C01BD04
ĐG : Pfizer Inc. , http://www.pfizer.com
CTHH: C19H27N3O5S2
PTK: 441.565
Dofetilide is a class III antiarrhythmic agent that is approved by the Food and Drug Administration (FDA) for the maintenance of sinus rhythm in individuals prone to the formation of atrial fibrillation and flutter, and for the chemical cardioversion to sinus rhythm from atrial fibrillation and flutter. [Wikipedia]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H27N3O5S2
Phân tử khối
441.565
Monoisotopic mass
441.139212369
InChI
InChI=1S/C19H27N3O5S2/c1-22(13-12-16-4-6-17(7-5-16)20-28(2,23)24)14-15-27-19-10-8-18(9-11-19)21-29(3,25)26/h4-11,20-21H,12-15H2,1-3H3
InChI Key
InChIKey=IXTMWRCNAAVVAI-UHFFFAOYSA-N
IUPAC Name
N-[4-(2-{[2-(4-methanesulfonamidophenoxy)ethyl](methyl)amino}ethyl)phenyl]methanesulfonamide
Traditional IUPAC Name
dofetilide
SMILES
CN(CCOC1=CC=C(NS(C)(=O)=O)C=C1)CCC1=CC=C(NS(C)(=O)=O)C=C1
Độ hòa tan
1.98e-02 g/l
logP
2.1
logS
-4.3
pKa (strongest acidic)
10.15
pKa (Strongest Basic)
8.99
PSA
104.81 Å2
Refractivity
113.27 m3·mol-1
Polarizability
46.03 Å3
Rotatable Bond Count
9
H Bond Acceptor Count
6
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Dofetilide is an antiarrhythmic drug with Class III (cardiac action potential duration prolonging) properties and is indicated for the maintenance of normal sinus rhythm. Dofetilide increases the monophasic action potential duration in a predictable, concentration-dependent manner, primarily due to delayed repolarization. At concentrations covering several orders of magnitude, Dofetilide blocks only IKr with no relevant block of the other repolarizing potassium currents (e.g., IKs, IK1). At clinically relevant concentrations, Dofetilide has no effect on sodium channels (associated with Class I effect), adrenergic alpha-receptors, or adrenergic beta-receptors.
Cơ Chế Tác Dụng : Dofetilide is a class III antiarrhythmic agent that is approved by the Food and Drug Administration (FDA) for the maintenance of sinus rhythm in individuals prone to the formation of atrial fibrillation and flutter, and for the chemical cardioversion to sinus rhythm from atrial fibrillation and flutter. [Wikipedia] The mechanism of action of Dofetilide is a blockade of the cardiac ion channel carrying the rapid component of the delayed rectifier potassium current, IKr. This inhibition of potassium channels results in a prolongation of action potential duration and the effective refractory period of accessory pathways (both anterograde and retrograde conduction in the accessory pathway).
Dược Động Học :
▧ Absorption :
>90%
▧ Volume of Distribution :
* 3 L/kg
▧ Protein binding :
60% -70%
▧ Metabolism :
Hepatic
▧ Half Life :
10 hours
Chỉ Định : For the maintenance of normal sinus rhythm (delay in time to recurrence of atrial fibrillation/atrial flutter [AF/AFl]) in patients with atrial fibrillation/atrial flutter of greater than one week duration who have been converted to normal sinus rhythm
Tương Tác Thuốc :
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Bendroflumethiazide Increased risk of cardiotoxicity and arrhythmias
  • Chlorothiazide Thiazide diuretics such as chlorothiazide may enhance the QTc-prolonging effect of dofetilide. Thiazide diuretics may increase the serum concentration of dofetilide. The concomitant use of hydrochlorothiazide and dofetilide is contraindicated by the manufacturer of dofetilide. Monitor for increased risk of QTc-prolongation and associated ventricular arrythmias during concomitant use of dofetilide and thiazide diuretics.
  • Chlorthalidone Increased risk of cardiotoxicity and arrythmias
  • Cimetidine Increases effect/toxicity of dofetilide
  • Clarithromycin Increased risk of cardiotoxicity and arrhythmias
  • Erythromycin Increased risk of cardiotoxicity and arrhythmias
  • Fingolimod Pharmacodynamic synergist. Contraindicated. Increased risk of bradycardia, AV block, and torsade de pointes.
  • Hydrochlorothiazide Increased risk of cardiotoxicity and arrhythmias
  • Indapamide Increased risk of cardiotoxicity and arrhythmias
  • Itraconazole This strong CYP3A4 inhibitor increases the effect and toxicity of dofetilide
  • Ketoconazole This strong CYP3A4 inhibitor increases the effect and toxicity of dofetilide
  • Mesoridazine Increased risk of cardiotoxicity and arrhythmias
  • Metolazone Increased risk of cardiotoxicity and arrhythmias
  • Quinupristin This combination presents an increased risk of toxicity
  • Ranolazine 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.
  • Telithromycin Increased risk of cardiotoxicity and arrhythmias
  • 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.
  • 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.
  • Trichlormethiazide Trichlormethiazide may increase Dofetilide serum concentrations and increase the QTc-prolonging effect of Dofetilide. Increased risk of ventricular arrhythmias.
  • Trimethoprim Trimethoprim may significantly reduced the clearance of Dofetilide. Trimethoprim is a cation transport inhibitor and may interfere with renal excretion of Dofetilide. Concomitant use is contraindicated.
  • Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Verapamil Verapamil may increase the plamsa levels of Dofetilide. Increased risk of torsade de pointes. Concomitant therapy is contraindicated.
  • Voriconazole Voriconazole may increase the serum concentration of dofetilide by decreasing its metabolism. 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 : Capsule - Oral
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Tikosyn
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00204
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=71329
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46509127
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07751
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00647
ChemSpider
http://www.chemspider.com/Chemical-Structure.64435.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0069-5800-43
PharmGKB
http://www.pharmgkb.org/drug/PA449389
Wikipedia
http://en.wikipedia.org/wiki/Dofetilide
RxList
http://www.rxlist.com/cgi/generic2/dofetilide.htm
Drugs.com
http://www.drugs.com/cdi/dofetilide.html
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