Tìm theo
Ospemifene
Các tên gọi khác (6 ) :
  • 2-(4-(4-Chloro-1,2-diphenyl-but-1-enyl)phenoxy)ethanol
  • 2-(P-((Z)-4-Chloro-1,2-diphenyl-1-butenyl)phenoxy)ethanol
  • Deamino-hydroxytoremifene
  • FC-1271
  • FC-1271a
  • Osphena
estrogen antagonists
Thuốc Gốc
Small Molecule
CAS: 128607-22-7
CTHH: C24H23ClO2
PTK: 378.891
Ospemifene is a new selective non-hormonal estrogen receptor modulator (SERM) that is used for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. FDA approved on February 26, 2013.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C24H23ClO2
Phân tử khối
378.891
Monoisotopic mass
378.138657687
InChI
InChI=1S/C24H23ClO2/c25-16-15-23(19-7-3-1-4-8-19)24(20-9-5-2-6-10-20)21-11-13-22(14-12-21)27-18-17-26/h1-14,26H,15-18H2/b24-23-
InChI Key
InChIKey=LUMKNAVTFCDUIE-VHXPQNKSSA-N
IUPAC Name
2-{4-[(1Z)-4-chloro-1,2-diphenylbut-1-en-1-yl]phenoxy}ethan-1-ol
Traditional IUPAC Name
ospemifene
SMILES
OCCOC1=CC=C(C=C1)C(=C(\CCCl)C1=CC=CC=C1)\C1=CC=CC=C1
Độ hòa tan
Insoluble
logP
5.56
logS
-5.9
pKa (strongest acidic)
15.1
pKa (Strongest Basic)
-2.8
PSA
29.46 Å2
Refractivity
121.68 m3·mol-1
Polarizability
41.97 Å3
Rotatable Bond Count
8
H Bond Acceptor Count
2
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : The half maximal inhibitory concentration (IC50) for estrogen receptor (ER) alpha and beta are 0.8 μM and 1.7 μM, respectively. Ospemifene has potential uses in the management of osteoporosis in postmenopausal women. It interacts with osteoblasts and osteoclasts in such a way that it reduces bone turnover. It also has potential uses in the prevention of breast cancer. Studies suggest that ospemifene, in a dose-dependent manner, reduces the incidence of tumours.
Cơ Chế Tác Dụng : Ospemifene is a new selective non-hormonal estrogen receptor modulator (SERM) that is used for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. FDA approved on February 26, 2013. Ospemifene is a next generation SERM (selective estrogen receptor modulator) that selectively binds to estrogen receptors and either stimulates or blocks estrogen's activity in different tissue types. It has an agonistic effect on the endometrium.
Dược Động Học :
▧ Absorption :
When a single oral dose of ospemifene 60 mg is given to postmenopausal women under fasted conditions, the pharmacokinetic parameters are as follows: Tmax = 2 hours (range of 1 - 8 hours); Cmax = 533 ng/mL; AUC (0-inf) = 4165 ng•hr/mL. When the same aforementioned dose is given to postmenopausal women under fed conditions, the pharmacokinetic parameters are as follows: Tmax = 2.5 hours (1 - 6 hours); Cmax = 1198 ng/mL; AUC (0-inf) = 7521 ng•hr/mL. Accumulation occurs following repeated doses. Time to steady state = 9 days. Although the bioavailability of ospemifene has not been formally evaluated, it is expected to have a low bioavailability because of its lipophilic nature.
▧ Volume of Distribution :
448 L
▧ Protein binding :
>99% bound to serum proteins
▧ Metabolism :
Ospemifene is hepatically metabolized via CYP3A4, CYP2C9, CYP2C19, and CYP2B6. The major metabolite was 4-hydroxyospemifene, 25% of the parent compound will undergo this biotransformation. Other metabolites include 4'-hydroxy-ospemifene, <7% of the parent compound will undergo this biotransformation. In order of decreasing potency, ospemifene was suggested to be a weak inhibitor for CYP2B6, CYP2C9, CYP2C19, CYP2C8, CYP2D6 and CYP3A4.
▧ Route of Elimination :
Following an oral administration of ospemifene, approximately 75% and 7% of the dose was excreted in feces and urine, respectively. Less than 0.2% of the ospemifene dose was excreted unchanged in urine.
▧ Half Life :
Terminal half-life = 26 hours .
▧ Clearance :
Total body clearance = 9.16 L/hr.
Độc Tính : Adverse reactions (≥1 percent) include: hot flush, vaginal discharge, muscle spasms, genital discharge, hyperhidrosis.
Chỉ Định : Ospemifene is used for the treatment of moderate to dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.
Tương Tác Thuốc :
  • Estradiol valerate/Dienogest Pharmacodynamic synergist; contraindicated.
  • Fluconazole Fluconazole, a moderate CYP3A / strong CYP2C9 / moderate CYP2C19 inhibitor, should not be used with ospemifene. Fluconazole increases the systemic exposure of ospemifene by 2.7-fold. Administration of fluconazole with ospemifene may increase the risk of adverse events.
  • Ketoconazole Ketoconazole, a strong CYP3A4 inhibitor increases the systemic exposure of ospemifene by 1.4-fold. Administration of ketoconazole chronically with ospemifene may increase the risk of OSPHENA-related adverse reactions.
  • Omeprazole Moderate CYP2C19 inhibitors may increase levels of ospemifene. Monitor concomitant therapy closely.
  • Rifampicin Rifampin, a strong CYP3A4 / moderate CYP2C9 / moderate CYP2C19 inducer, decreases the systemic exposure of ospemifene by 58%. Therefore, co-administration of ospemifene with drugs such as rifampin which induce CYP3A4, CYP2C9 and/or CYP2C19 activity would be expected to decrease the systemic exposure of ospemifene, which may decrease the clinical effect.
Liều Lượng & Cách Dùng : Tablet - Oral - 60 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB04938
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3036505
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=10048556
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D08958
ChemSpider
http://www.chemspider.com/Chemical-Structure.2300501.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/59630-580-00
Wikipedia
http://en.wikipedia.org/wiki/Ospemifene
RxList
http://www.rxlist.com/osphena-drug.htm
Drugs.com
http://www.drugs.com/osphena.html
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