Source of information: Drugbank (External Link). Last updated on: 3rd July 18
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Active Ingredient / Synonyms
Mirabegron | Mirabegron |
Mirabegron is a beta-3 adrenergic receptor agonist for the management of overactive bladder. It is an alternative to antimuscarinic drugs for this indication. FDA approved on June 28, 2012.
Mirabegron is a beta-3 adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.
Mechanism of Action
Mirabegron is a potent and selective agonist for beta-3 adrenergic receptors. Once beta-3 receptors are activated, the detrusor smooth muscle relaxes to allow for a larger bladder capacity. At higher doses (200 mg), there is a potential for mirabegron to activate beta-1 and beta-2 adrenergic receptors.
Mirabegron has little effect on the mean maximum flow rate or mean detrusor pressure at maximum flow rate in patients with lower urinary tract symptoms and bladder outlet obstruction. Furthermore, mirabegron increases blood pressure in a dose dependent manner. However, this effect is reversible when mirabegron is discontinued. Mirabegron also increases heart rate in a dose dependent manner. The dose in which half-maximal efficacy is demonstrated is 25 mg. Comparatively, the dose in which maximal efficacy is demonstrated is 100 mg.
The absolute bioavailability increases from 29% at a dose of 25 mg to 35% at a dose of 50 mg. Mean Cmax and AUC increase more than dose proportionally. This relationship is more apparent at doses above 50 mg. Females generally have a lower magnitude of increase of Cmax and AUCtau compared to males when doses of mirabegron doubles or quadruples. Steady state concentrations are achieved within 7 days of once daily dosing with mirabegron. After once daily administration, plasma exposure of mirabegron at steady state is approximately double that seen after a single dose. Tmax, oral dose, healthy subjects= 3.5 hours;
Vd, steady state, IV dose = 1670 L. This high value suggests that mirabegron is extensively distributed in the body.
Mirabegron is metabolized via multiple pathways involving dealkylation, oxidation, (direct) glucuronidation, and amide hydrolysis. The major circulating entity is mirabegron. Two major and inactive metabolites (phase 2 glucuronides) are produced. Although mirabegron is a substrate for CYP2D6 and CYP3A4, its role in the elimination of the drug is limited. Studies also suggest that CYP3A4 is the main enzyme that facilitates the oxidative metabolism of the drug. Furthermore, butylcholinesterase, uridine diphospho-glucuronosyltransferases (UGT), and possibly alcohol dehydrogenase may be involved with the metabolism of mirabegron.
Mirabegron is eliminated via urine (radiolabeled drug: 55%; unchanged drug: ~25%) and feces (radiolabeled drug: 34%; unchanged drug: 0%). Renal elimination of mirabegron is primarily through active tubular secretion and glomerular filtration. Extent of elimination via urine is dose-dependent.
Terminal elimination half-life = 50 hours
Total body clearance (CLtot), IV dose = 57 L/h; Renal clearance (CLR) = 13 L/h
Most commonly reported adverse reactions (> 2% and > placebo) were hypertension, nasopharyngitis, urinary tract infection and headache
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