Tìm theo
Darifenacin
Các tên gọi khác (5 ) :
  • (S)-1-(2-(2,3-dihydro-5-Benzofuranyl)ethyl)-alpha,alpha-diphenyl-3-pyrrolidineacetamide
  • Darifenacin
  • Darifenacina
  • Darifénacine
  • Darifenacinum
antispasmodic agents
Thuốc Gốc
Small Molecule
CAS: 133099-04-4
ATC: G04BD10
ĐG : Lake Erie Medical and Surgical Supply
CTHH: C28H30N2O2
PTK: 426.55
Darifenacin (Enablex®, Novartis) is a medication used to treat urinary incontinence. Darifenacin works by blocking the M3 muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions. It thereby decreases the urgency to urinate. It should not be used in people with urinary retention. It is not known whether this selectivity for the M3 receptor translates into any clinical advantage when treating symptoms of overactive bladder syndrome.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C28H30N2O2
Phân tử khối
426.55
Monoisotopic mass
426.230728214
InChI
InChI=1S/C28H30N2O2/c29-27(31)28(23-7-3-1-4-8-23,24-9-5-2-6-10-24)25-14-17-30(20-25)16-13-21-11-12-26-22(19-21)15-18-32-26/h1-12,19,25H,13-18,20H2,(H2,29,31)/t25-/m1/s1
InChI Key
InChIKey=HXGBXQDTNZMWGS-RUZDIDTESA-N
IUPAC Name
2-[(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-diphenylacetamide
Traditional IUPAC Name
darifenacin
SMILES
NC(=O)C([C@@H]1CCN(CCC2=CC3=C(OCC3)C=C2)C1)(C1=CC=CC=C1)C1=CC=CC=C1
Độ hòa tan
2.98e-04 g/l
logP
4.5
logS
-6.2
pKa (strongest acidic)
16.21
pKa (Strongest Basic)
10.11
PSA
55.56 Å2
Refractivity
128.37 m3·mol-1
Polarizability
48.54 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
3
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
5
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : Darifenacin is a competitive muscarinic receptor antagonist. In vitro studies using human recombinant muscarinic receptor subtypes show that darifenacin has greater affinity for the M3 receptor than for the other known muscarinic receptors (9 and 12-fold greater affinity for M3 compared to M1 and M5, respectively, and 59-fold greater affinity for M3 compared to both M2 and M4). Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of the urinary bladder smooth muscle and stimulation of salivary secretion. Adverse drug effects such as dry mouth, constipation and abnormal vision may be mediated through effects on M3 receptors in these organs.
Cơ Chế Tác Dụng : Darifenacin (Enablex®, Novartis) is a medication used to treat urinary incontinence. Darifenacin works by blocking the M3 muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions. It thereby decreases the urgency to urinate. It should not be used in people with urinary retention. It is not known whether this selectivity for the M3 receptor translates into any clinical advantage when treating symptoms of overactive bladder syndrome. Darifenacin selectively antagonizes the muscarinic M3 receptor. M3 receptors are involved in contraction of human bladder and gastrointestinal smooth muscle, saliva production, and iris sphincter function.
Dược Động Học :
▧ Absorption :
The mean oral bioavailability at steady state is estimated to be 15% and 19% for 7.5 mg and 15 mg tablets, respectively.
▧ Volume of Distribution :
* 163 L
▧ Protein binding :
Darifenacin is approximately 98% bound to plasma proteins (primarily to alpha-1-acid-glycoprotein).
▧ Metabolism :
Hepatic. Primarily mediated by the cytochrome P450 enzymes CYP2D6 and CYP3A4.
▧ Half Life :
The elimination half-life of darifenacin following chronic dosing is approximately 13-19 hours.
▧ Clearance :
* 40 L/h [extensive metabolizers] * 32 L/h [poor metabolizers]
Độc Tính : Overdosage can potentially result in severe central anticholinergic effects.
Chỉ Định : For the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency.
Tương Tác Thuốc :
  • Clarithromycin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
  • Donepezil Possible antagonism of action
  • Galantamine Possible antagonism of action
  • Itraconazole This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
  • Ketoconazole This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
  • Nefazodone This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
  • Nelfinavir Nelfinavir, a strong CYP3A4 inhibitor, may decrease the metabolism of darifenacin/solifenacin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of darifenacin if nelfinavir is initiated, discontinued or dose changed.
  • Ritonavir This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
  • Rivastigmine Possible antagonism of action
  • Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Darifenacin, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
  • Tamoxifen Darifenacin may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
  • Tamsulosin Darifenacin, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Darifenacin is initiated, discontinued, or dose changed.
  • Telithromycin Telithromycin may reduce clearance of Darifenacin. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Darifenacin if Telithromycin is initiated, discontinued or dose changed.
  • Tramadol Darifenacin may decrease the effect of Tramadol by decreasing active metabolite production.
  • Triprolidine Triprolidine and Darifenacin, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Trospium Trospium and Darifenacin, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of darifenacin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of darifenacin if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Tablet, extended release - Oral
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Novartis
    Sản phẩm biệt dược : Emselex
  • Công ty : Warner Chilcott
    Sản phẩm biệt dược : Enablex
  • Công ty : Dr. Reddy's
    Sản phẩm biệt dược : Xelena
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00496
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=444031
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508104
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D01699
ChemSpider
http://www.chemspider.com/Chemical-Structure.392054.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50109647
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0078-0419-15
PharmGKB
http://www.pharmgkb.org/drug/PA164774901
Wikipedia
http://en.wikipedia.org/wiki/Darifenacin
RxList
http://www.rxlist.com/cgi/generic3/enablex.htm
Drugs.com
http://www.drugs.com/cdi/darifenacin-extended-release-tablets.html
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