What is INGREZZA?
INGREZZA, with the generic name valbenazine, is a prescription medication approved to treat adults with tardive dyskinesia and chorea associated with Huntington’s disease. Tardive dyskinesia (TD) is a movement disorder characterized by involuntary, repetitive movements, most often in the face, that can occur with long-term use of certain psychiatric medications. Chorea involves involuntary, jerky movements. As a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, INGREZZA is believed to work by blocking a protein transporter in nerve cells that regulates the release of neurotransmitters, particularly dopamine. By inhibiting VMAT2, INGREZZA can reduce the amount of dopamine released into the synapse, which is thought to be responsible for the uncontrolled movements associated with these conditions.
The Half-Life of INGREZZA: Valbenazine and its Active Metabolite
The half-life is a fundamental pharmacokinetic parameter that describes the time required for the concentration of a substance in the body to decrease to half of its initial value. For INGREZZA, or valbenazine, understanding the half-life is made more complex by the fact that it is a prodrug. This means it is converted in the body into an active form.
Research indicates that the half-life for both valbenazine and its primary active metabolite, [+]-α-dihydrotetrabenazine (DTBZ), falls within the range of 15 to 22 hours. This relatively consistent half-life for both the parent drug and its active form is crucial for the medication's effectiveness and its once-daily dosing schedule. The therapeutic effects are primarily mediated by the active metabolite, meaning its sustained presence is key to controlling movement symptoms.
Valbenazine's Metabolism and Elimination Pathway
Following oral administration, INGREZZA is extensively metabolized. The primary metabolic pathways involve hydrolysis of the valine ester and oxidative metabolism mediated by cytochrome P450 (CYP) enzymes, particularly CYP3A4/5. This process converts the prodrug valbenazine into its active metabolite, DTBZ. DTBZ is then further metabolized, in part, by the enzyme CYP2D6. The liver is the main site for this metabolic activity.
Once metabolized, the drug is primarily eliminated from the body through excretion. Approximately 60% of the administered dose is excreted in the urine, while about 30% is eliminated via feces. Less than 2% is excreted as unchanged valbenazine or its active metabolite, indicating the body's efficiency in breaking down the compound.
How Long Does INGREZZA Stay in the System?
Based on its half-life of 15 to 22 hours, it generally takes about five half-lives for a medication to be almost completely eliminated from the body. For INGREZZA, this translates to an estimated elimination time of about 3 to 4.5 days following a single dose. However, this is an estimate, and the actual time can be influenced by various individual factors.
Factors Influencing INGREZZA's Half-Life
Several factors can affect an individual's half-life and clearance of INGREZZA, potentially altering the time it takes to leave the system. These include:
- Liver Function: The liver is crucial for metabolizing valbenazine. Patients with moderate or severe liver impairment may have slower drug clearance, requiring a dose adjustment as directed by a healthcare professional.
- Genetics: Genetic variations in the CYP450 enzyme system, especially for CYP2D6, can affect how quickly the drug's metabolite is processed. Individuals who are CYP2D6 poor metabolizers may require dose adjustments.
- Drug Interactions: Taking other medications that are strong inhibitors of CYP3A4 or CYP2D6 can interfere with INGREZZA's metabolism, potentially prolonging its half-life.
- Age and Health: An individual's overall health, kidney function, and age can also play a role in drug clearance.
Comparison of VMAT2 Inhibitors: INGREZZA vs. Austedo
INGREZZA is not the only VMAT2 inhibitor on the market. Austedo (deutetrabenazine) is another medication used for similar conditions. A comparison of their key pharmacological characteristics can help illustrate their differences.
| Feature | INGREZZA (Valbenazine) | Austedo (Deutetrabenazine) |
|---|---|---|
| Active Ingredient | Valbenazine | Deutetrabenazine |
| Mechanism | VMAT2 Inhibitor | VMAT2 Inhibitor |
| Active Metabolite | [+]-α-dihydrotetrabenazine (DTBZ) | DTBZ (similar to INGREZZA) |
| Half-Life | 15–22 hours (for valbenazine and DTBZ) | Significantly longer due to deuterium substitution |
| Dosing | Typically once daily | Typically twice daily |
| Metabolism | Primarily CYP3A4/5, then CYP2D6 for metabolite | Slower metabolism due to deuterium, resulting in longer half-life |
| Approval | Tardive Dyskinesia, Huntington's Chorea | Tardive Dyskinesia, Huntington's Chorea |
Clinical Relevance of Half-Life in Dosing
The half-life of INGREZZA is a major determinant of its clinical use. The 15–22 hour half-life supports a once-daily dosing regimen, which can improve patient adherence. By taking the medication at the same time each day, a relatively stable concentration of the drug and its active metabolite is maintained in the body, which is known as a steady state. It takes approximately one week (about five half-lives) to reach this steady state, at which point the medication's full therapeutic effect can be observed. Adjustments to the dose, especially in cases of hepatic impairment or when other drugs interfere with metabolism, are based on this pharmacokinetic profile.
Conclusion
In conclusion, the half-life of INGREZZA (valbenazine) and its active metabolite, DTBZ, is between 15 and 22 hours, a key factor supporting its convenient once-daily dosing. This pharmacokinetic property ensures a consistent therapeutic effect while the drug is slowly but effectively cleared from the body over a period of 3 to 4.5 days. Understanding this half-life, along with individual factors like liver function and genetics, is vital for managing treatment effectively and ensuring patient safety. Regular monitoring and adherence to a doctor's instructions are essential to maximize benefits and minimize risks associated with the medication. For more detailed prescribing information, consult the INGREZZA package insert provided by the manufacturer.
A list of metabolic components:
- Hydrolysis: The initial breakdown of valbenazine.
- CYP3A4/5: Primary cytochrome P450 enzymes involved in oxidizing valbenazine.
- DTBZ: The active metabolite formed from valbenazine, also with a half-life of 15–22 hours.
- CYP2D6: Enzyme responsible for further metabolism of the active metabolite DTBZ.
- Inactive Metabolites: The ultimate breakdown products that are excreted from the body.
Administration details:
- Frequency: Typically taken once daily.
- Food Intake: Can be taken with or without food.
- Sprinkle Capsules: An alternative formulation (INGREZZA Sprinkle) can be mixed with soft food.
Disclaimer: This information is for general knowledge and should not be taken as medical advice. Consult with a healthcare professional before starting any new supplement regimen.
