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
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
9
H Bond Acceptor Count
5
H Bond Donor Count
4
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học :
Cơ Chế Tác Dụng :
Dược Động Học :
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 :
Chỉ Định :
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
-
Sản phẩm biệt dược : Betanis
-
Sản phẩm biệt dược : Metmiga
-
Công ty : Astellas PharmaSản phẩm biệt dược : Myrbetriq
Tài Liệu Tham Khảo Thêm
drugbank
National Drug Code Directory
Wikipedia
Drugs.com
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