|Drug class||Class III antiarrhythmic|
|Main uses||Atrial fibrillation, atrial flutter|
|Side effects||Palpitations, low blood pressure, nausea, headache|
|Typical dose||1 gram|
|Elimination half-life||6 hours (2-12 hours)|
|Excretion||Kidney (82%), fecal|
|Chemical and physical data|
|Molar mass||384.58 g·mol−1|
|3D model (JSmol)|
Relatively common side effects include palpitations, low blood pressure, nausea, and headache. Other side effects may include torsades de pointes and AV block. Safety in pregnancy is unclear. It is a class III antiarrhythmic and works by prolonging the action potential.
Ibutilide was approved for medical use in the United States in 1995. It is approved in part of Europe but not the United Kingdom. In the United States it costs about 325 USD for a 1 mg dose as of 2021.
Administration resulted in successful heart rhythm control in 31-44% of patients within 90 minutes, with sustained polymorphic ventricular tachycardia in 0.9-2.5% of patients. It appears to show better results in atrial flutter as compared to atrial fibrillation.
In those who weight more than 60 kg the typical dose is 1 mg while in those under 60 kg the dose is 10 mcg/kg.
Like other antiarrhythmics, ibutilide can lead to abnormal heart rhythms due to its ability to prolong the QT interval, which can lead to the potentially fatal abnormal heart rhythm known as torsades de pointes. Consequently, the drug is contraindicated in patients that are likely to develop abnormal heart rhythms; this includes persons that have had polymorphic ventricular tachycardia in the past, have a long QT interval, sick sinus syndrome, or a recent myocardial infarction, among others.
Mechanism of action
Ibutilide, like other class III antiarrhythmic drugs, blocks delayed rectified potassium current.
It does have action on the slow sodium channel and promotes the influx of sodium through these slow channels.
Although potassium current seems to play a role, their interactions are complex and not well understood. Ibutilide's unique mechanism works by an activation of a specific inward sodium current, thus producing its therapeutic response in which a prolonged action potential increases myocytes’ cardiac refractoriness in case of atrial fibrillation and flutter.
Ibutilide is intravenously administered. It has a high first-pass metabolism, which results in a poor bioavailability when taken orally. Individual pharmacokinetic properties are highly viable during the clinical trial.
Ibutilide has a relatively large volume of distribution among individual subjects, which is about 11L/kg. Approximately 40% of the drug is bound with plasma albumin of healthy volunteers in a trial. This is also approximately close to patients with atrial fibrillation and flutter.
Ibutilide has a high systemic plasma clearance that closes to the hepatic blood flow (29mL/min/kg). Its metabolic pathway is via liver's cytochrome P450 system by isoenzymes other than CYP3A4 and CYP2D6 by which the heptyl side chain of ibutilide is oxidized. With eight metabolites are detected in the urine, however, only one is an active metabolite that shares the similar electrophysiologic property of the Class III antiarrhythmic agents. The plasma concentration of this metabolite is only less than 10% of ibutilide.
After administration of ibutilide, it is quickly excreted by renal pathway with a half-life of approximately 6 hours. Approximately 82% of a 0.01 mg/kg dose is excreted in the urine during the trial. Among those, around 7% is excreted as unchanged drug. The remainder of the drug is excreted in feces (about 19%).
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