In a study with antimuscarinic drugs, more DDIs were investigated using a model of Rhesus monkeys. Dose combinations of vibegron and tolterodine showed increased bladder capacity, the effects of both drugs at low dosis strengthened each other, known as synergism. The addition of darifenacin to vibegron created greater bladder relaxation only when used at high doses. Additionally, co-administration with Imidafenacin shows an increase in bladder capacity and voided volume in comparison to monotherapy. Possibly, a widely adapted treatment will be the combination of beta-3-adrenergic agonist with a nonselective M2/M3 antagonist as the most prevalent option.Clinical studies show no significant drug–drug interaction (DDI), aside from a serum concentration increase of digoxin when taken with vibegron. Maximal concentrations and systemic exposure (Cmax and area under the curve (AUC)) of digoxin are both increased as a result of DDI. Apart from the no to little DDIs, Vibegron has an additional safety quality in that it does not cross the blood-brain barrier and therefore does not induce cognitive impairment. Furthermore, Vibegron can be taken with or without food, this does not have an effect on vibegron plasma concentrations. Toxicity
Effects on animals
Pregnant rats were given very high daily oral doses of Vibegron during the period of organogenesis and showed no embryo-fetal developmental toxicity up to 300 mg/kg/day. Similar data was found in rabbits. Maternal toxicity was observed when doses exceeded 100 mg/kg/day in lactating rats. Clinical studies show that Vibegron is not toxic, safe and well-tolerated in patients. References
External links
"Vibegron". Drug Information Portal. U.S. National Library of Medicine.
It was globally approved on September 21, 2018, in Japan for OAB.Vibegron has been proven effective in 5 key clinical trials.A phase IIb global trial completed in 2013 of 1395 patients, of which 89.7% were women and 63.3% had not been treated previously, demonstrated a significant decrease in daily micturitions and urgent urinary incontinence episodes upon administration of vibegron.An international phase III trial of 506 participants completed in 2019 found statistically significant efficacy of vibegron after 2 weeks of daily administration. The adverse effect rates in patients treated with vibegron were comparable to those in patients who received a placebo.GEMTESA, a drug using vibegron as an active ingredient was approved by the FDA on December 23, 2020, after an additional phase III international trial of 1085 patients. Society and culture
Legal status
Vibegron was approved for medical use in the United States in December 2020. Names
Vibegron is the international nonproprietary name (INN). Mechanism of action
Vibegron is a selective agonist for the beta-3 adrenergic receptor (β3-AR). The receptors are located in the kidneys, urinary tract and bladder tissue. Upon binding, the β3 receptor undergoes a conformational change. This induces the activation of adenylate cyclases via G proteins and thereby promotes the formation of cyclic adenosine monophosphate (cAMP). The consequence of this cascade is an increased intracellular cAMP concentration which triggers activation of cAMP-dependent protein kinase A and causes a reduction of Ca2+ concentration in the cytoplasm. The kinase then phosphorylates myosin chains and thereby inhibits muscle contraction.The final effect of vibegron is muscle relaxation in the bladder.