Dofetilide

Dofetilide

Clinical data
AHFS/Drugs.com	Monograph
MedlinePlus	a601235
ATC code	C01BD04 (WHO)
Pharmacokinetic data
Bioavailability	96% (oral)
Protein binding	60% -70%
Biological half-life	10 hours
Identifiers
IUPAC name N-[4-(2-{[2-(4-methane sulfonamidophenoxy)ethyl] (methyl)amino}ethyl)phenyl]methanesulfonamide
CAS Number	115256-11-6 Y
PubChem (CID)	71329
IUPHAR/BPS	2604
DrugBank	DB00204 Y
ChemSpider	64435 Y
UNII	R4Z9X1N2ND Y
KEGG	D00647 Y
ChEBI	CHEBI:4681 Y
ChEMBL	CHEMBL473 Y
ECHA InfoCard	100.166.441
Chemical and physical data
Formula	C19H27N3O5S2
Molar mass	441.567 g/mol
3D model (Jmol)	Interactive image
SMILES O=S(=O)(Nc1ccc(cc1)CCN(CCOc2ccc(cc2)NS(=O)(=O)C)C)C
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 Y Key:IXTMWRCNAAVVAI-UHFFFAOYSA-N Y

Dofetilide is a class III antiarrhythmic agent. It is marketed under the trade name Tikosyn by Pfizer, and is available in the United States in capsules containing 125, 250, and 500 µg of dofetilide. It is not available in Europe or Australia.

Due to the pro-arrhythmic potential of dofetilide, it is only available by prescription from physicians who have undergone specific training in the risks of treatment with dofetilide. In addition, it is only available by mail order or through specially trained local pharmacies.

Dofetilide is used for the maintenance of sinus rhythm in individuals prone to the occurrence of atrial fibrillation and flutter arrhythmias, and for chemical cardioversion to sinus rhythm from atrial fibrillation and flutter.

Dofetilide is well absorbed in its oral form, with a bioavailability of >90%.

The elimination half-life of dofetilide is roughly 10 hours; however, this varies based on many physiologic factors (most significantly creatinine clearance), and ranges from 4.8 to 13.5 hours. Due to the significant level of renal elimination (80% unchanged, 20% metabolites), the dose of dofetilide must be adjusted to prevent toxicity due to impaired renal function.

Dofetilide works by selectively blocking the rapid component of the delayed rectifier outward potassium current (I_Kr).

This causes the refractory period of atrial tissue to increase, hence its effectiveness in the treatment of atrial fibrillation and atrial flutter.

Dofetilide does not affect V_max (the slope of the upstroke of phase 0 depolarization), conduction velocity, or the resting membrane potential.

There is a dose-dependent increase in the QT interval and the corrected QT interval (QTc). Because of this, many practitioners will initiate dofetilide therapy only on individuals under telemetry monitoring or if serial EKG measurements of QT and QTc can be performed.