Mirabegron

Các tên gọi khác (1) :

Myrbetriq

muscle relaxants genitourinary

Thuốc Gốc

Small Molecule

CAS: 223673-61-8

ATC: G04BD12

CTHH: C₂₁H₂₄N₄O₂S

PTK: 396.506

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.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₁H₂₄N₄O₂S

Phân tử khối

396.506

Monoisotopic mass

396.161996722

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

InChI Key

InChIKey=PBAPPPCECJKMCM-IBGZPJMESA-N

IUPAC Name

2-(2-amino-1,3-thiazol-4-yl)-N-[4-(2-{[(2R)-2-hydroxy-2-phenylethyl]amino}ethyl)phenyl]acetamide

Traditional IUPAC Name

mirabegron

SMILES

NC1=NC(CC(=O)NC2=CC=C(CCNC[C@H](O)C3=CC=CC=C3)C=C2)=CS1

Độ hòa tan

Insoluble

logP

2.89

logS

-5

pKa (strongest acidic)

13.84

pKa (Strongest Basic)

9.62

PSA

100.27 Å²

Refractivity

113.23 m³·mol^-1

Polarizability

44.2 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Rule of Five

true

Ghose Filter

true

MDDR-Like Rule

true

Dược Lực Học : 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.

Cơ Chế Tác Dụng : 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 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.

Dược Động Học :

▧ 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

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

Chỉ Định : 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.

Tương Tác Thuốc :

Desipramine Mirabegron is a moderate CYP2D6 inhibitor and may cause an increase in exposure of CYP2D6 substrates. Monitor concomitant therapy closely.
Digoxin Mirabegron increased Cmax and AUC of digoxin. Initiate therapy with digoxin at lowest possible dose. Monitor concomitant therapy closely.
Flecainide Mirabegron is a moderate CYP2D6 inhibitor and may cause an increase in exposure of CYP2D6 substrates. Monitor concomitant therapy closely.
Ketoconazole Concomitant therapy with p-glycoprotein and strong CYP3A4 inhibitors may increase levels of mirabegron. Monitor concomitant therapy closely.
Metoprolol Mirabegron is a moderate CYP2D6 inhibitor and may cause an increase in exposure of CYP2D6 substrates. Monitor concomitant therapy closely.
Propafenone Mirabegron is a moderate CYP2D6 inhibitor and may cause an increase in exposure of CYP2D6 substrates. Monitor concomitant therapy closely.
Rifampicin Strong CYP3A4 inducers may decrease levels of mirabegron. Monitor concomitant therapy closely.
Thioridazine Mirabegron is a moderate CYP2D6 inhibitor and may cause an increase in exposure of CYP2D6 substrates. Monitor concomitant therapy closely.
Warfarin Mirabegron increased Cmax and AUC of S- and R-warfarin. Monitor concomitant therapy closely.

Liều Lượng & Cách Dùng : Tablet, extended release - Oral - 25 mg, 50 mg

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty :

Sản phẩm biệt dược : Betanis
Công ty :

Sản phẩm biệt dược : Metmiga
Công ty : Astellas Pharma

Sản phẩm biệt dược : Myrbetriq

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB08893

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D09535

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0469-2602-30

Wikipedia

http://en.wikipedia.org/wiki/Mirabegron

RxList

http://www.rxlist.com/myrbetriq-drug.htm

Drugs.com

http://www.drugs.com/cdi/mirabegron.html

Bạn thấy hài lòng ?

Bạn chưa hài lòng ?

... loading