Vernakalant API Manufacturers

General Description:

Vernakalant, identified by CAS number 794466-70-9, is a notable compound with significant therapeutic applications. 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.

Indications:

This drug is primarily indicated for: 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. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Vernakalant undergoes metabolic processing primarily in: Vernakalant is mainly eliminated by CYP2D6 mediated O-demethylation in CYP2D6 extensive metabolisers. Glucuronidation is the main metabolism pathway in CYP2D6 poor metabolisers. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Vernakalant are crucial for its therapeutic efficacy: 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 . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Vernakalant is an important consideration for its dosing schedule: Elimination half life in CYP2D6 extensive metabolizers is 3 hours and 5.5 hours in poor metabolizers. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Vernakalant exhibits a strong affinity for binding with plasma proteins: Displays low protein binding and the free fraction of vernakalant in human serum is 53-63% at concentration range of 1-5 μg/ml. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Vernakalant from the body primarily occurs through: Mainly eliminated via renal excretion. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Vernakalant is distributed throughout the body with a volume of distribution of: Approximately 2L/kg. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Vernakalant is a critical factor in determining its safe and effective dosage: The typical total body clearance of vernakalant was estimated to be 0.41 l/hr/kg. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Vernakalant exerts its therapeutic effects through: 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. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Vernakalant functions by: Vernakalant blocks atrial voltage-gated sodium channels in a dose and frequency-dependent manner and inhibits late sodium current (INa)which confers its effect on intra-atrial conduction. This current blockade enhance and onset of drug action accelerates in higher heart rate as the affinity of vernakalant for INa also increases. Its binding offset is quick once the heart rate slows . It also blocks Kv 1.5 channel and its early activating potassium channels (IKur) and inhibits acetylcholine-activated potassium channels (IKAch), which are specific to the atrium and cause prolongation of atrial refractoriness. Vernakalant also blocks Kv4.3 channel and its cardiac transient outward potassium current (Ito), which is involved more with atrial than ventricular refractoriness . Vernakalant minimally blocks hERG channels and its rapidly activating/delayed rectifying potassium current (IKr) which accounts for mild QT prolongation. QRS widening due to INa blockade also contributes to QT prolongation . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Vernakalant belongs to the class of organic compounds known as tyrosols and derivatives. These are compounds containing a hydroxyethyl group attached to the C4 carbon of a phenol group, classified under the direct parent group Tyrosols and derivatives. This compound is a part of the Organic compounds, falling under the Benzenoids superclass, and categorized within the Phenols class, specifically within the Tyrosols and derivatives subclass.

Categories:

Vernakalant is categorized under the following therapeutic classes: Antiarrhythmic agents, Antiarrhythmics, Class III, Benzene Derivatives, Cardiac Therapy, Cytochrome P-450 CYP2D6 Inhibitors, Cytochrome P-450 CYP2D6 Inhibitors (strength unknown), Cytochrome P-450 CYP2D6 Substrates, Cytochrome P-450 Enzyme Inhibitors, Cytochrome P-450 Substrates, Ethers, Methyl Ethers, Phenols, Phenyl Ethers, Potential QTc-Prolonging Agents, QTc Prolonging Agents. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.