Tìm theo
Raloxifene
Các tên gọi khác (7 ) :
  • (2-(4-Hydroxyphenyl)-6-hydroxybenzo(b)thien-3-yl)(4-(2-(1-piperidinyl)ethoxy)phenyl)methanone
  • Keoxifene
  • LY 139481
  • RAL
  • Raloxifene
  • Raloxifeno
  • Raloxifenum
Thuốc giảm đau, hạ sốt, chống viêm không steroid, điều trị Gút và các bệnh xương khớp
Thuốc Gốc
Small Molecule
CAS: 84449-90-1
ATC: G03XC01
ĐG : AQ Pharmaceuticals Inc. , http://www.aqpharmaceuticals.com
CTHH: C28H27NO4S
PTK: 473.583
A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C28H27NO4S
Phân tử khối
473.583
Monoisotopic mass
473.166079047
InChI
InChI=1S/C28H27NO4S/c30-21-8-4-20(5-9-21)28-26(24-13-10-22(31)18-25(24)34-28)27(32)19-6-11-23(12-7-19)33-17-16-29-14-2-1-3-15-29/h4-13,18,30-31H,1-3,14-17H2
InChI Key
InChIKey=GZUITABIAKMVPG-UHFFFAOYSA-N
IUPAC Name
2-(4-hydroxyphenyl)-3-({4-[2-(piperidin-1-yl)ethoxy]phenyl}carbonyl)-1-benzothiophen-6-ol
Traditional IUPAC Name
raloxifene
SMILES
OC1=CC=C(C=C1)C1=C(C(=O)C2=CC=C(OCCN3CCCCC3)C=C2)C2=C(S1)C=C(O)C=C2
Độ tan chảy
143-147 °C
Độ hòa tan
0.25mg/L
logP
5.2
logS
-6
pKa (strongest acidic)
8.89
pKa (Strongest Basic)
7.95
PSA
70 Å2
Refractivity
135.48 m3·mol-1
Polarizability
52.55 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
5
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
5
Bioavailability
1
MDDR-Like Rule
true
Dược Lực Học : Raloxifene, a selective estrogen receptor modulator (SERM) of the benzothiophene class, is similar to tamoxifen in that it produces estrogen-like effects on bone and lipid metabolism, while antagonizing the effects of estrogen on breast and uterine tissue. Raloxifene differs chemically and pharmacologically from naturally occuring estrogens, synthetic steroidal and nonsteroidal compounds with estrogenic activity, and antiestrogens. Estrogens play an important role in the reproductive, skeletal, cardiovascular, and central nervous systems in women, and act principally by regulating gene expression. When estrogen binds to a ligand-binding domain of the estrogen receptor, biologic response is initiated as a result of a conformational change of the estrogen receptor, which leads to gene transcription through specific estrogen response elements of target gene promoters. The subsequent activation or repression of the target gene is mediated through 2 distinct transactivation domains of the receptor: AF-1 and AF-2. The estrogen receptor also mediates gene transcription using different response elements and other signalling pathways. The role of estrogen as a regulator of bone mass is well established. In postmenopausal women, the progressive loss of bone mass is related to decreased ovarian function and a reduction in the level of circulation estrogens. Estrogen also has favourable effects on blood cholesterol.
Cơ Chế Tác Dụng : A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [PubChem] Raloxifene binds to estrogen receptors, resulting in differential expression of multiple estrogen-regulated genes in different tissues. Raloxifene produces estrogen-like effects on bone, reducing resorption of bone and increasing bone mineral density in postmenopausal women, thus slowing the rate of bone loss. The maintenance of bone mass by raloxifene and estrogens is, in part, through the regulation of the gene-encoding transforming growth factor-β3 (TGF-β3), which is a bone matrix protein with antiosteoclastic properties. Raloxifene activates TGF-β3 through pathways that are estrogen receptor-mediated but involve DNA sequences distinct from the estrogen response element. The drug also binds to the estrogen receptor and acts as an estrogen agonist in preosteoclastic cells, which results in the inhibtion of their proliferative capacity. This inhibition is thought to contribute to the drug's effect on bone resorption. Other mechanisms include the suppression of activity of the bone-resorbing cytokine interleukin-6 promoter activity. Raloxifene also antagonizes the effects of estrogen on mammary tissue and blocks uterotrophic responses to estrogen. By competing with estrogens for the estrogen receptors in reproductive tissue, raloxifene prevents the transcriptional activation of genes containing the estrogen response element. As well, raloxifene inhibits the estradiol-dependent proliferation of MCF-7 human mammary tumor cells in vitro. The mechansim of action of raloxifene has not been fully determined, but evidence suggests that the drug's tissue-specific estrogen agonist or antagonist activity is related to the structural differences between the raloxifene-estrogen receptor complex (specifically the surface topography of AF-2) and the estrogen-estrogen receptor complex. Also, the existence of at least 2 estrogen receptors (ERα, ERβ) may contribute to the tissue specificity of raloxifene.
Dược Động Học :
▧ Absorption :
Approximately 60% of an oral dose is absorbed, but presystemic glucuronide conjugation is extensive. Absolute bioavailability of raloxifene is 2.0%
▧ Volume of Distribution :
* 2348 L/kg [oral administration of single doses ranging from 30 to 150 mg]
▧ Protein binding :
95%
▧ Metabolism :
Hepatic, raloxifene undergoes extensive first-pass metabolism to the glucuronide conjugates: raloxifene-4'-glucuronide, raloxifene-6-glucuronide, and raloxifene-6, 4'-diglucuronide. No other metabolites have been detected, providing strong evidence that raloxifene is not metabolized by cytochrome P450 pathways
▧ Route of Elimination :
Raloxifene is primarily excreted in feces, and less than 0.2% is excreted unchanged in urine.
▧ Half Life :
27.7
▧ Clearance :
* 44.1 L/kg•hr [Healthy Postmenopausal Woman with Single Dose] * 47.4 L/kg•hr [Healthy Postmenopausal Woman with Multiple Dose] * Oral cl=44.1 L/kg•hr
Chỉ Định : For the prevention and treatment of osteoporosis in post-menopausal women, as well as prevention and treatment of corticosteroid-induced bone loss. Also for the reduction in the incidence of invasive breast cancer in postmenopausal women with osteoporosis or have a high risk for developing breast cancer.
Tương Tác Thuốc :
  • Chlorotrianisene Association not recommended
  • Cholestyramine The resin decreases the effect of raloxifene
  • Clomifene Association not recommended
  • Colesevelam Bile Acid Sequestrants may decrease the absorption of Raloxifene. It would seem prudent to separate the doses of raloxifene and bile acid sequestrants by at least 2 hours. The manufacturer of raloxifene recommends against coadministration of these agents.1 The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.
  • Colestipol The resin decreases the effect of raloxifene
  • Conjugated Estrogens Association not recommended
  • Diethylstilbestrol Association not recommended
  • Estradiol Association not recommended
  • Estriol Association not recommended
  • Estropipate Association not recommended
  • Ethinyl Estradiol Association not recommended
  • Levothyroxine Raloxifene decreases absorption of levothyroxine
  • Mestranol Association not recommended
Liều Lượng & Cách Dùng : Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Evista 60 mg tablet
    Giá bán buôn : USD >4.37
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Evista
  • Công ty :
    Sản phẩm biệt dược : Keoxifene
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00481
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5035
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506514
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07228
ChemSpider
http://www.chemspider.com/Chemical-Structure.4859.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=19441
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0002-4165-02
PharmGKB
http://www.pharmgkb.org/drug/PA451221
Wikipedia
http://en.wikipedia.org/wiki/Raloxifene
RxList
http://www.rxlist.com/cgi/generic/raloxif.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/evi1169.shtml
Drugs.com
http://www.drugs.com/cdi/raloxifene.html
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