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Valbenazine API Manufacturers & Suppliers

General Description:

Valbenazine, identified by CAS number 1025504-45-3, is a notable compound with significant therapeutic applications. Valbenazine (development name NBI-98854) has been used in trials studying the treatment and basic science of Tourette Syndrome and Tardive Dyskinesia. In April, 2017, valbenazine was approved by the FDA (as Ingrezza) as the first and only approved treatment for adults with Tardive Dyskinesia (TD).

Indications:

This drug is primarily indicated for: For the treatment of tardive dyskinesia in adults . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Valbenazine undergoes metabolic processing primarily in: Valbenzine is extensively metabolized to one active metabolite -α-dihydrotetrabenazine (-α-HTBZ) through hydrolysis of the valine ester reaching Cmax within 4-8 hours . It is also metabolized via oxidation by CYP3A4/5 to a mono-oxidzed metabolite NBI-136110 which also appears to pharmacologically active. -α-HTBZ is metabolized by CYP2D6. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Valbenazine are crucial for its therapeutic efficacy: Oral bioavailability of 49% . Tmax of 0.5-1h. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Valbenazine is an important consideration for its dosing schedule: Both valbenazine and its active metabolite -α-HTBZ have a half life of 15-22 hours . This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Valbenazine exhibits a strong affinity for binding with plasma proteins: Valbenazine is >99% bound to plasma proteins . Its active metabolite -α-HTBZ is 64% bound to plasma proteins. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Valbenazine from the body primarily occurs through: Roughly 60% is excreted in urine and 30% in feces . Less than 2% if the parent compound or active metabolite was excreted unchanged. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Valbenazine is distributed throughout the body with a volume of distribution of: 92 Liters . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Valbenazine is a critical factor in determining its safe and effective dosage: 7.2 Liters/hour . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Valbenazine exerts its therapeutic effects through: Valbenazine decreases the availability of monoamine neurotransmitters by preventing their storage in synaptic vesicles . This is believed to be the reason behind its therapeutic effect in tardive dyskinesia although the exact mechanism is unknown. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Valbenazine functions by: Valbenazine and its active meabolites bind to and inhibit vesicular monoamine transporter 2 (VMAT2)with high selectivity (valbenazine Ki = 150nM, -α-HTBZ Ki = 1.98nM, NBI136110 Ki = 160nM) with no significant binding to VMAT1 (Ki <10microM for each) . This prevents the reuptake and storage of monoamine neurotransmitters noradrenaline, dopamine, and serotonin in synaptic vesicles making them vulnerable to metabolism by cytosolic enzymes. The presynaptic release of monoamine neurotransmitters is decreased due to the lack of vesicles with packaged neurotransmitter ready for release into the synapse. Neither valbenazine nor its active metabolite exhibit significant off target binding at dopamine, serotonin, or adrenaline receptors or uptake transporters at 10microM concentrations. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Valbenazine belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids, classified under the direct parent group Alpha amino acid esters. This compound is a part of the Organic compounds, falling under the Organic acids and derivatives superclass, and categorized within the Carboxylic acids and derivatives class, specifically within the Amino acids, peptides, and analogues subclass.

Categories:

Valbenazine is categorized under the following therapeutic classes: Amino Acids, Amino Acids, Branched-Chain, Amino Acids, Peptides, and Proteins, Cytochrome P-450 CYP2D6 Substrates, Cytochrome P-450 CYP3A Substrates, Cytochrome P-450 CYP3A4 Substrates, Cytochrome P-450 CYP3A5 Substrates, Cytochrome P-450 Substrates, Drugs that are Mainly Renally Excreted, Heterocyclic Compounds, Fused-Ring, Nervous System, Quinolizines, Vesicular Monoamine Transporter 2 Inhibitor, Vesicular Monoamine Transporter 2 Inhibitors. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.