Vemakalant

Absorption

In patients, average peak plasma concentrations of vernakalant were 3.9 μg/ml following a single 10 minute infusion of 3 mg/kg vernakalant hydrochloride, and 4.3 μg/ml following a second infusion of 2 mg/kg with a 15 minute interval between doses .

Toxicity

Some common unwanted effects include hypotension, ventricular arrhythmias, bradycardia, atrial flutter, dysgeusia, paraesthesia, dizziness and nausea.

Description

Vernakalant is a potassium channel blocker that was approved in Europe in 2010 for treatment of atrial fibrillation (AF), a condition of cardiac arrhythmia in which the atria of the heart beat irregularly due to changes in cardiac ion channel function and distribution. Vernakalant has activity for cardiac Na+ and K+ channels and also for the atrial-selective Kv1.5 channel. Vernakalant (RSD1235) was characterized in animal models to assess efficacy, atrial selectivity, and reduction in side effects.

Originator

Cardiome Pharma Corp. (Canada)

Indications

Indicated for the rapid conversion of recent onset of atrial fibrillation to sinus rhythm in adults for non-surgery patients that lasts for less than 7 days of duration and post-cardiac surgery patients with atrial fibrillation lasting less than 3 days of duration.

Background

Vernakalant was developed by Cardiome Pharma as as an antiarrhythmic drug intended for rapid conversion of atrial fibrillation to sinus rhythm. It acts as an atypical class III antiarrhythmic drug that potentiates its effect in higher heart rates. Intravenous formulation was approved in Europe in September 2010 as Brinavess and in Canada in April 2017. It is an investigational drug under regulatory review by FDA.

Definition

ChEBI: Vernakalant is an alcohol and a member of phenols.

brand name

Brinavess

Pharmacokinetics

Vernakalant blocks currents in all phases of atrial action potential including atria-specific potassium currents (the ultra-rapid delayed rectifier and the acetylcholine dependent potassium currents) and prolongs the refractory period. It dose-dependently prolongs atrial refractoriness, prolongs AV nodal conduction and refractoriness, and slightly prolongs QRS duration without significantly affecting ventricular refractory period. Vernakalant has a high affinity to ion channels specifically involved in repolarization of atrial tissue and is thought to have a low proarrhythmic potential.

Metabolism

Vernakalant is mainly eliminated by CYP2D6 mediated O-demethylation in CYP2D6 extensive metabolisers. Glucuronidation is the main metabolism pathway in CYP2D6 poor metabolisers.