化合物信息

Drug Groups

approved

Description

Ibutilide is a Class III antiarrhythmic agent that is indicated for acute cardioconversion of atrial fibrillation and atrial flutter of a recent onset to sinus rhythm. [Wikipedia]

Indication

Indicated for the rapid conversion of atrial fibrillation or atrial flutter of recent onset to sinus rhythm.

Pharmacology

Ibutilide prolongs the action potential duration and increases both atrial and ventricular refractoriness in vivo, i.e., class III electrophysiologic effects. Voltage clamp studies indicate that ibutilide, at nanomolar concentrations, delays repolarization by activation of a slow, inward current (predominantly sodium), rather than by blocking outward potassium currents, which is the mechanism by which most other class III antiarrhythmics act.

Toxicity

Acute overdose in animals results in CNS toxicity; notably, CNS depression, rapid gasping breathing, and convulsions. The intravenous median lethal dose in the rat was more than 50 mg/kg which is, on a mg/m² basis, at least 250 times the maximum recommended human dose.

Affected Organisms

Biotransformation

Primarily hepatic. Eight metabolites of ibutilide were detected in metabolic profiling of urine. These metabolites are thought to be formed primarily by o-oxidation followed by sequential b-oxidation of the heptyl side chain of ibutilide. Of the eight metabolites, only the o-hydroxy metabolite possesses class III electrophysiologic properties similar to that of ibutilide in an in vitro isolated rabbit myocardium model.

Absorption

Rapid after intravenous injection

Half Life

6 hours (ranges from 2-12 hours)

Protein Binding

40%

Elimination

In healthy male volunteers, about 82% of a 0.01 mg/kg dose of [14C] ibutilide fumarate was excreted in the urine (about 7% of the dose as unchanged ibutilide) and the remainder (about 19%) was recovered in the feces.

Distribution

* 11 L/kg

Clearance

* 29 mL/min/kg

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