Vibegronum
Vibegronum Uses, Dosage, Side Effects, Food Interaction and all others data.
Vibegronum is a potent, selective beta-3 adrenergic receptor (β3) agonist that relaxes the detrusor smooth muscle of the bladder, thereby increasing bladder capacity. Vibegronum was first approved in Japan in September 2018 for the treatment of overactive bladder, a condition associated with distressing symptoms of urge urinary incontinence, urgency, and urinary frequency, and reduced quality of life of patients. On December 23, 2020, vibegron was approved for the same indication in adults. It is available as oral tablets under the market name GEMTESA.
Vibegronum is the second beta-3 adrenergic agonist approved for the treatment of overactive bladder following mirabegron, which was approved in 2012. Unlike mirabegron, vibegron is less likely to be associated with drug-drug interactions involving the CYP3A4, 2D6, or 2C9 enzymes.
Vibegronum selectivity for beta-3 adrenergic receptors is >9000 times higher than for β1AR or β2AR. Vibegronum improves clinical symptoms of overactive bladder by increasing bladder capacity without affecting bladder contraction. It significantly increases the functional bladder volume in a dose-dependent manner, which results in prolongation of the interval between voids. In clinical studies, vibegron inhibited detrusor bladder contractions in a concentration-dependent manner, reduced voiding pressure, and increased bladder compliance. In Japanese clinical studies comprising patients with overactive bladder, vibegron significantly improved the frequency of micturition, urgency, and urgency incontinence episodes.
| Trade Name | Vibegronum |
| Availability | Prescription only |
| Generic | Vibegron |
| Vibegron Other Names | Vibegron, Vibégron, Vibegrón, Vibegronum |
| Related Drugs | solifenacin, Botox, VESIcare, Gemtesa, darifenacin, Enablex |
| Type | |
| Formula | C26H28N4O3 |
| Weight | Average: 444.535 Monoisotopic: 444.216140778 |
| Protein binding | Vibegron is 49.6–51.3% bound to human plasma proteins. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Vibegronum is a beta-3 adrenergic agonist the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults.
Vibegronum is indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults.
Vibegronum is also used to associated treatment for these conditions: Urinary Bladder, Overactive
How Vibegronum works
Overactive bladder is characterized by symptoms of urge urinary incontinence, urgency, and urinary frequency. Bladder filling and emptying are regulated by the coordinated communication between sympathetic and parasympathetic systems. Bladder filling occurs via parasympathetic inhibition and the sympathetic hypogastric nerve releasing norepinephrine, which acts on beta-adrenergic receptors responsible for mediating detrusor muscle relaxation. Symptoms of overactive bladder are thought to be caused by the deterioration of the sensory connections between the bladder, spinal cord and brain, leading to changes in the lower urinary tract and abnormal bladder sensations of the urge to void at small bladder volumes.
Beta-3 adrenergic receptors (β3ARs) are expressed in the kidneys and lower urinary tract, including ureters, urethra, prostate, and bladder. Vibegronum is a selective agonist at β3AR. One vibegron binds to the receptor, β3AR is stimulated and undergoes a conformation change and activates adenylyl cyclases (AC), which promotes the formation of cyclic adenosine monophosphate (cAMP). Increased intracellular cAMP concentration leads to the activation of cAMP-dependent protein kinase A (PKA), which subsequently phosphorylates myosin light chains that are responsible for inhibiting the interaction of actin with myosin dependent on calcium – calmodulin complex. In clinical trials, vibegron increased cAMP levels in a dose-proportional manner. There is evidence that β3AR agonists may also work via sensory mechanisms without directly affecting detrusor muscle motor function.
Toxicity
There is limited clinical information on overdose from vibegron. In the case of a suspected drug overdose, supportive and symptomatic treatment should be initiated.
Food Interaction
- Take with or without food. A high-fat meal had no clinically significant effects on vibegron plasma concentrations.
Vibegronum Disease Interaction
Volume of Distribution
The mean apparent volume of distribution is 6304 L. The average blood-to-plasma concentration ratio is 0.9. According to tissue distribution studies in animals, vibegron does not penetrate the blood-brain barrier, suggesting limited potential for CNS toxicity in humans.
Elimination Route
The mean Tmax is 1-3 hours. Steady-state concentrations are achieved within 7 days of once-daily dosing.
Half Life
The terminal plasma half-life ranges from 60 to 70 hours. The effective half-life is 30.8 hours.
Clearance
There is limited information on the clearance rate of vibegron.
Elimination Route
In a radiolabeled drug study, approximately 59% of the radiolabeled dose was recovered in feces, in which 54% of that amount was in the unchanged parent drug form. About 20% of the radioactivity was recovered in urine, in which 19% of the amount was in the unchanged form.
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