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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/07 06:32:39」(JST)

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Raloxifene (marketed as Evista by Eli Lilly and Company) is an oral selective estrogen receptor modulator (SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. It is used in the prevention of osteoporosis in postmenopausal women and to reduce the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer.^[2]

Medical use

Raloxifene is indicated for the treatment and prevention of osteoporosis in postmenopausal women. It is also used for reduction of risk and treatment of invasive breast cancer, and it also reduces breast density.^[3] For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate.

Adverse reactions

Common adverse events considered to be drug-related were hot flashes and leg cramps.^{[citation needed]}

Raloxifene may infrequently cause serious blood clots to form in the legs, lungs, or eyes. Other reactions experienced include leg swelling/pain, trouble breathing, chest pain, vision changes. Raloxifene is a teratogenic drug, i.e., can cause developmental abnormalities such as birth defects.

Black box warnings were added to the label of raloxifine in 2007 warning of increased risk of death due to stroke for postmenopausal women with documented coronary heart disease or at increased risk for major coronary events, as well as increased risks for deep vein thrombosis and pulmonary embolism.^[4]

A report in September 2009 from Health and Human Services' Agency for Healthcare Research and Quality suggests that tamoxifen and raloxifene, used to treat breast cancer, significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects.^[5]

Contradications and precautions

Raloxifene is contraindicated in lactating women or women who are or may become pregnant, in women with active or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis and in women known to be hypersensitive to raloxifene.^[4]

Pharmacology

SERMs mimic estrogen in some tissues and have anti-estrogen activity in others.^[4]

Bottle of Raloxifene

Physical and chemical properties

Raloxifene hydrochloride (HCl) has the empirical formula C₂₈H₂₇NO₄S•HCl, which corresponds to a molecular weight of 510.05 g/mol. Raloxifene HCl is an off-white to pale-yellow solid that is slightly soluble in water.^[4]

Society and culture

An editorial in Lancet Oncology criticized the way that information about the drug was released.^[6]

References

^ Jeong, Eun Ju; Liu, Yong; Lin, Huimin; Hu, Ming (2005-03-15). "Species- and Disposition Model-Dependent Metabolism of Raloxifene in Gut and Liver: Role of UGT1A10". Drug Metabolism and Disposition ( ASPET) 33 (6): 785–794. doi:10.1124/dmd.104.001883. PMID 15769887. Retrieved 2010-10-20.
^ "FDA Approves New Uses for Evista" (Press release). U.S. Food and Drug Administration. 2007-09-14. Retrieved 2007-09-15.
^ Jeon-Hor, Chen et al. (September 15, 2003). "Reduction of Breast Density Following Tamoxifen Treatment Evaluated by 3-D MRI: Preliminary Study". Magn Reson Imaging. doi:10.1016/j.mri.2010.07.009. Retrieved March 30, 2013.
^ ^a ^b ^c ^d Raloxifene label Last updated 09/2007]
^ OncoGenetics.Org (September 2009). "Medications Effective in Reducing Risk of Breast Cancer But Increase Risk of Adverse Effects". OncoGenetics.Org. Retrieved 2009-09-14. ^{[dead link]}
^ Thelancetoncology, (2006). "A STARring role for raloxifene?". Lancet Oncol 7 (6): 443. doi:10.1016/S1470-2045(06)70701-X. PMID 16750489.

External links

STAR: a head-to-head comparison of tamoxifen and raloxifene as breast-cancer preventatives
Full Prescribing Information
Position paper of the National Women's Health Network
Heringa M (2003). "Review on raloxifene: profile of a selective estrogen receptor modulator". Int J Clin Pharmacol Ther 41 (8): 331–45. PMID 12940590.
Barrett-Connor E (2001). "Raloxifene: risks and benefits". Ann N Y Acad Sci 949: 295–303. doi:10.1111/j.1749-6632.2001.tb04036.x. PMID 11795366.

UpToDate Contents

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1. 骨粗鬆症に対する選択的エストロゲン受容体調節剤 selective estrogen receptor modulators for osteoporosis
2. 慢性腎臓病患者における骨粗鬆症：診断、評価およびマネージメント osteoporosis in patients with chronic kidney disease diagnosis evaluation and management
3. 乳癌予防のための選択的エストロゲン受容体調節因子およびアロマターゼ阻害剤 selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention
4. 選択的エストロゲン受容体モジュレーターの作用機序 mechanisms of action of selective estrogen receptor modulators
5. がん予防 cancer prevention

English Journal

In vivo reference point indentation reveals positive effects of raloxifene on mechanical properties following 6months of treatment in skeletally mature beagle dogs.

Aref M, Gallant MA, Organ JM, Wallace JM, Newman CL, Burr DB, Brown DM, Allen MR.SourceDepartment of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Bone.Bone.2013 Oct;56(2):449-53. doi: 10.1016/j.bone.2013.07.009. Epub 2013 Jul 17.
Raloxifene treatment has been shown previously to positively affect bone mechanical properties following 1year of treatment in skeletally mature dogs. Reference point indentation (RPI) can be used for in vivo assessment of mechanical properties and has been shown to produce values that are highly co
PMID 23871851

Evaluation of rhesus monkey and Guinea pig hepatic cytosol fractions as models for human aldehyde oxidase.

Choughule KV, Barr JT, Jones JP.SourceDepartment of Chemistry, Washington State University, Pullman, Washington.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2013 Oct;41(10):1852-8. doi: 10.1124/dmd.113.052985. Epub 2013 Aug 5.
Aldehyde oxidase (AOX) is a cytosolic enzyme expressed across a wide range of species, including guinea pig and rhesus monkey. These species are believed to be the best preclinical models for studying human AOX-mediated metabolism. We compared AOX activity in rhesus monkeys, guinea pigs, and humans
PMID 23918666

Modulation of bone turnover in orchidectomized rats treated with raloxifene and risedronate.

Khedr NF, El-Ashmawy NE, El-Bahrawy HA, Haggag AA, El-Abd EE.SourceDepartment of Biochemistry, Faculty of Pharmacy, Tanta University, Gharbia, 31527, Egypt.
Fundamental & clinical pharmacology.Fundam Clin Pharmacol.2013 Oct;27(5):526-34. doi: 10.1111/j.1472-8206.2012.01047.x. Epub 2012 Jul 4.
Osteoporosis is a reduction in bone mineral density (BMD). It develops less often in men than in women. This study aimed to evaluate the bone protective effects of raloxifene (RAL), risedronate (RIS), and their combination on osteoporotic male rats. Forty male Wister rats (12 weeks) were randomly d
PMID 22762129

Japanese Journal

Effects of Selective Estrogen Receptor Modulators on Plasma Membrane Estrogen Receptors and Catecholamine Synthesis and Secretion in Cultured Bovine Adrenal Medullary Cells

Inagaki Hirohide,Toyohira Yumiko,Takahashi Keita [他]
Journal of pharmacological sciences 124(1), 66-75, 2014-01
NAID 40019948983

Effects of Selective Estrogen Receptor Modulators on Plasma Membrane Estrogen Receptors and Catecholamine Synthesis and Secretion in Cultured Bovine Adrenal Medullary Cells

Inagaki Hirohide,Toyohira Yumiko,Takahashi Keita,Ueno Susumu,Obara Go,Kawagoe Toshinori,Tsutsui Masato,Hachisuga Toru,Yanagihara Nobuyuki
Journal of Pharmacological Sciences 124(1), 66-75, 2014
… Here we report the effects of raloxifene and tamoxifen, selective estrogen receptor modulators, on plasma membrane estrogen receptors and catecholamine synthesis and secretion in these cells. … Raloxifene caused dual effects on the specific binding of [3H]17β-estradiol to the plasma membranes isolated from bovine adrenal medulla; …
NAID 130003382627

O.li.v.e. PLUS SERMに関する最新論文の要約と解説バゼドキシフェンとラロキシフェンの骨折抑制効果の比較 : FRAXにより算出された骨折リスク別の椎体骨折,非椎体骨折,および全臨床骨折に対する有効性に関する検討

太田博明 [要約と解説]
O.li.v.e. : osteo lipid vascular & endocrinology : 骨代謝と生活習慣病の連関 3(2), 118-124, 2013-05
NAID 40019740973

Related Pictures

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★リンクテーブル★

リンク元	「ラロキシフェン」
拡張検索	「raloxifene hydrochloride」

「ラロキシフェン」

Raloxifene
Systematic (IUPAC) name
	[6-hydroxy-2-(4-hydroxyphenyl)- benzothiophen-3-yl]- [4-[2-(1-piperidyl)ethoxy]phenyl] -methanone
Clinical data
Trade names	Evista
AHFS/Drugs.com	monograph
MedlinePlus	a698007
Licence data	EMA:Link, US FDA:link
Pregnancy; category	AU: X (High risk); US: X (Contraindicated);
Legal status	℞ (Prescription only);
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	2%
Protein binding	95%
Metabolism	Gut glucuronidation; CYP system not involved
Biological half-life	27.7 hours
Excretion	Fecal
Identifiers
CAS Registry Number	84449-90-1
ATC code	G03XC01
PubChem	CID: 5035
IUPHAR/BPS	2820
DrugBank	DB00481
ChemSpider	4859
UNII	YX9162EO3I
ChEBI	CHEBI:8772
ChEMBL	CHEMBL81
PDB ligand ID	RAL (PDBe, RCSB PDB)
Chemical data
Formula	C28H27NO4S
Molecular mass	473.584 g/mol
	SMILES O=C(c1c3ccc(O)cc3sc1c2ccc(O)cc2)c5ccc(OCCN4CCCCC4)cc5 ;
	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 ; Key:GZUITABIAKMVPG-UHFFFAOYSA-N ;
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