Identification

Name
Mirabegron
Accession Number
DB08893
Description

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.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 396.506
Monoisotopic: 396.161996722
Chemical Formula
C21H24N4O2S
Synonyms
  • Mirabegron
External IDs
  • YM-178
  • YM178

Pharmacology

Indication

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.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

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.

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.

TargetActionsOrganism
ABeta-3 adrenergic receptor
agonist
Humans
Absorption

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;

Volume of distribution

Vd, steady state, IV dose = 1670 L. This high value suggests that mirabegron is extensively distributed in the body.

Protein binding

71% bound to plasma proteins. It binds to albumin and alpha-1-acid glycoprotein with moderate affinity.

Metabolism

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.

Route of elimination

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.

Half-life

Terminal elimination half-life = 50 hours

Clearance

Total body clearance (CLtot), IV dose = 57 L/h; Renal clearance (CLR) = 13 L/h

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Most commonly reported adverse reactions (> 2% and > placebo) were hypertension, nasopharyngitis, urinary tract infection and headache

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Mirabegron which could result in a higher serum level.
AbametapirThe serum concentration of Mirabegron can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Mirabegron can be increased when combined with Abatacept.
AbirateroneThe metabolism of Mirabegron can be decreased when combined with Abiraterone.
AcarboseAcarbose may decrease the excretion rate of Mirabegron which could result in a higher serum level.
AcebutololThe metabolism of Mirabegron can be decreased when combined with Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of Mirabegron which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Mirabegron which could result in a higher serum level.
AcetaminophenThe metabolism of Mirabegron can be decreased when combined with Acetaminophen.
AcetazolamideAcetazolamide may increase the excretion rate of Mirabegron which could result in a lower serum level and potentially a reduction in efficacy.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with or without food. Food decreases drug absorption, but not to a clinically significant extent.

Products

Product Images
International/Other Brands
Betanis / Metmiga
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BetmigaTablet, extended release50 mgOralAstellas Pharma Europe Bv2012-12-20Not applicableEU flag
BetmigaTablet, extended release25 mgOralAstellas Pharma Europe Bv2012-12-20Not applicableEU flag
BetmigaTablet, extended release25 mgOralAstellas Pharma Europe Bv2012-12-20Not applicableEU flag
BetmigaTablet, extended release50 mgOralAstellas Pharma Europe Bv2012-12-20Not applicableEU flag
BetmigaTablet, extended release50 mgOralAstellas Pharma Europe Bv2012-12-20Not applicableEU flag
BetmigaTablet, extended release50 mgOralAstellas Pharma Europe Bv2012-12-20Not applicableEU flag
BetmigaTablet, extended release50 mgOralAstellas Pharma Europe Bv2012-12-20Not applicableEU flag
BetmigaTablet, extended release25 mgOralAstellas Pharma Europe Bv2012-12-20Not applicableEU flag
BetmigaTablet, extended release25 mgOralAstellas Pharma Europe Bv2012-12-20Not applicableEU flag
BetmigaTablet, extended release25 mgOralAstellas Pharma Europe Bv2012-12-20Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
G04BD12 — Mirabegron
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as anilides. These are organic heterocyclic compounds derived from oxoacids RkE(=O)l(OH)m (l not 0) by replacing an OH group by the NHPh group or derivative formed by ring substitution.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Anilides
Alternative Parents
Phenethylamines / N-arylamides / 2,4-disubstituted thiazoles / Aralkylamines / 2-amino-1,3-thiazoles / Heteroaromatic compounds / 1,2-aminoalcohols / Amino acids and derivatives / Secondary alcohols / Secondary carboxylic acid amides
show 8 more
Substituents
1,2-aminoalcohol / 1,3-thiazol-2-amine / 2,4-disubstituted 1,3-thiazole / Alcohol / Amine / Amino acid or derivatives / Anilide / Aralkylamine / Aromatic alcohol / Aromatic heteromonocyclic compound
show 22 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monocarboxylic acid amide, 1,3-thiazole, aromatic amide, ethanolamines (CHEBI:65349)

Chemical Identifiers

UNII
MVR3JL3B2V
CAS number
223673-61-8
InChI Key
PBAPPPCECJKMCM-IBGZPJMESA-N
InChI
InChI=1S/C21H24N4O2S/c22-21-25-18(14-28-21)12-20(27)24-17-8-6-15(7-9-17)10-11-23-13-19(26)16-4-2-1-3-5-16/h1-9,14,19,23,26H,10-13H2,(H2,22,25)(H,24,27)/t19-/m0/s1
IUPAC Name
2-(2-amino-1,3-thiazol-4-yl)-N-[4-(2-{[(2R)-2-hydroxy-2-phenylethyl]amino}ethyl)phenyl]acetamide
SMILES
NC1=NC(CC(=O)NC2=CC=C(CCNC[[email protected]](O)C3=CC=CC=C3)C=C2)=CS1

References

General References
  1. Takasu T, Ukai M, Sato S, Matsui T, Nagase I, Maruyama T, Sasamata M, Miyata K, Uchida H, Yamaguchi O: Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J Pharmacol Exp Ther. 2007 May;321(2):642-7. Epub 2007 Feb 9. [PubMed:17293563]
  2. Kashyap M, Tyagi P: The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy option. Expert Opin Drug Metab Toxicol. 2013 May;9(5):617-27. doi: 10.1517/17425255.2013.786700. Epub 2013 Apr 4. [PubMed:23550899]
KEGG Drug
D09535
PubChem Compound
9865528
PubChem Substance
175427137
ChemSpider
8041219
RxNav
1300786
ChEBI
65349
ChEMBL
CHEMBL2095212
ZINC
ZINC000001996784
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Mirabegron
AHFS Codes
  • 86:12.08.12 — Selective Beta 3-adrenergic Agonists
FDA label
Download (510 KB)
MSDS
Download (481 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of Mirabegron and Tolterodine1
4CompletedNot AvailableUrinary Bladder, Overactive1
4CompletedTreatmentBenign Prostatic Hyperplasia (BPH) / Urinary Bladder, Overactive1
4CompletedTreatmentDisseminated Sclerosis1
4CompletedTreatmentImpaired Cognition / Parkinson's Disease (PD) / Urinary Bladder, Overactive1
4CompletedTreatmentUrinary Bladder, Overactive7
4CompletedTreatmentUrinary Incontinence, Urge1
4Not Yet RecruitingTreatmentBenign Prostatic Hyperplasia (BPH) / Urinary Bladder, Overactive1
4RecruitingBasic ScienceFood Effect / Healthy Chinese Subjects / Pharmacokinetics of Mirabegron1
4RecruitingPreventionDementias / Lower Urinary Tract Symptoms (LUTS) / Urinary Bladder, Overactive / Urinary Incontinence, Urge1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, extended releaseOral25 mg
Tablet, extended releaseOral50 mg
Tablet, film coatedOral25 mg
Tablet, film coatedOral50 mg
Tablet
Tablet, film coated, extended releaseOral25 mg/1
Tablet, film coated, extended releaseOral50 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2305802No2008-11-182018-10-15Canada flag
CA2464068No2007-10-162022-10-29Canada flag
CA2503570No2023-11-042011-04-19Canada flag
USRE44872No2014-04-292023-12-18US flag
US7750029No2010-07-062023-12-18US flag
US6346532No2002-02-122018-10-15US flag
US8835474No2014-09-162023-11-04US flag
US6562375No2003-05-132020-08-01US flag
US7982049No2011-07-192023-11-04US flag
US7342117No2008-03-112023-11-04US flag
US8772315No2014-07-082028-10-30US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsoluble FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.00412 mg/mLALOGPS
logP2.2ALOGPS
logP2.89ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)13.84ChemAxon
pKa (Strongest Basic)9.62ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area100.27 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity113.23 m3·mol-1ChemAxon
Polarizability44.2 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9398
Blood Brain Barrier+0.8115
Caco-2 permeable-0.6462
P-glycoprotein substrateSubstrate0.5567
P-glycoprotein inhibitor INon-inhibitor0.8492
P-glycoprotein inhibitor IINon-inhibitor0.8487
Renal organic cation transporterNon-inhibitor0.7223
CYP450 2C9 substrateNon-substrate0.7656
CYP450 2D6 substrateNon-substrate0.7786
CYP450 3A4 substrateNon-substrate0.641
CYP450 1A2 substrateNon-inhibitor0.5904
CYP450 2C9 inhibitorInhibitor0.6156
CYP450 2D6 inhibitorNon-inhibitor0.8873
CYP450 2C19 inhibitorNon-inhibitor0.574
CYP450 3A4 inhibitorInhibitor0.5223
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5711
Ames testNon AMES toxic0.6422
CarcinogenicityNon-carcinogens0.8972
BiodegradationNot ready biodegradable0.5977
Rat acute toxicity2.4527 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9094
hERG inhibition (predictor II)Inhibitor0.567
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004j-0429000000-a1fa6e47b60253c53578

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
Gene Name
ADRB3
Uniprot ID
P13945
Uniprot Name
Beta-3 adrenergic receptor
Molecular Weight
43518.615 Da
References
  1. Kashyap M, Tyagi P: The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy option. Expert Opin Drug Metab Toxicol. 2013 May;9(5):617-27. doi: 10.1517/17425255.2013.786700. Epub 2013 Apr 4. [PubMed:23550899]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Lee J, Moy S, Meijer J, Krauwinkel W, Sawamoto T, Kerbusch V, Kowalski D, Roy M, Marion A, Takusagawa S, van Gelderen M, Keirns J: Role of cytochrome p450 isoenzymes 3A and 2D6 in the in vivo metabolism of mirabegron, a beta3-adrenoceptor agonist. Clin Drug Investig. 2013 Jun;33(6):429-40. doi: 10.1007/s40261-013-0084-y. [PubMed:23625188]
  2. Takusagawa S, Yajima K, Miyashita A, Uehara S, Iwatsubo T, Usui T: Identification of human cytochrome P450 isoforms and esterases involved in the metabolism of mirabegron, a potent and selective beta3-adrenoceptor agonist. Xenobiotica. 2012 Oct;42(10):957-67. doi: 10.3109/00498254.2012.675095. Epub 2012 Apr 18. [PubMed:22509825]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Lee J, Moy S, Meijer J, Krauwinkel W, Sawamoto T, Kerbusch V, Kowalski D, Roy M, Marion A, Takusagawa S, van Gelderen M, Keirns J: Role of cytochrome p450 isoenzymes 3A and 2D6 in the in vivo metabolism of mirabegron, a beta3-adrenoceptor agonist. Clin Drug Investig. 2013 Jun;33(6):429-40. doi: 10.1007/s40261-013-0084-y. [PubMed:23625188]
  2. Takusagawa S, Yajima K, Miyashita A, Uehara S, Iwatsubo T, Usui T: Identification of human cytochrome P450 isoforms and esterases involved in the metabolism of mirabegron, a potent and selective beta3-adrenoceptor agonist. Xenobiotica. 2012 Oct;42(10):957-67. doi: 10.3109/00498254.2012.675095. Epub 2012 Apr 18. [PubMed:22509825]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Takusagawa S, Yajima K, Miyashita A, Uehara S, Iwatsubo T, Usui T: Identification of human cytochrome P450 isoforms and esterases involved in the metabolism of mirabegron, a potent and selective beta3-adrenoceptor agonist. Xenobiotica. 2012 Oct;42(10):957-67. doi: 10.3109/00498254.2012.675095. Epub 2012 Apr 18. [PubMed:22509825]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Mirabegron inhibited P-gp-mediated drug transport at high concentrations, according to the FDA Label.
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Takusagawa S, Ushigome F, Nemoto H, Takahashi Y, Li Q, Kerbusch V, Miyashita A, Iwatsubo T, Usui T: Intestinal absorption mechanism of mirabegron, a potent and selective beta(3)-adrenoceptor agonist: involvement of human efflux and/or influx transport systems. Mol Pharm. 2013 May 6;10(5):1783-94. doi: 10.1021/mp300582s. Epub 2013 Apr 24. [PubMed:23560393]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Takusagawa S, Ushigome F, Nemoto H, Takahashi Y, Li Q, Kerbusch V, Miyashita A, Iwatsubo T, Usui T: Intestinal absorption mechanism of mirabegron, a potent and selective beta(3)-adrenoceptor agonist: involvement of human efflux and/or influx transport systems. Mol Pharm. 2013 May 6;10(5):1783-94. doi: 10.1021/mp300582s. Epub 2013 Apr 24. [PubMed:23560393]

Drug created on May 30, 2013 23:44 / Updated on September 24, 2020 02:08

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