用户名： 密   码：
注册 | 忘记密码？
药品详细

Tamoxifen(他莫昔芬)

化学结构式图
中文名
他莫昔芬
英文名
Tamoxifen
分子式
C26H29NO
化学名
(2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine
分子量
Average: 371.5146
Monoisotopic: 371.224914555
CAS号
10540-29-1
ATC分类
L02B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

One of the selective estrogen receptor modulators with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the endometrium. [PubChem]

生产厂家
  • Aegis pharmaceuticals inc
  • Astrazeneca pharmaceuticals lp
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Pharmachemie bv
  • Rosemont group ltd
  • Roxane laboratories inc
  • Teva pharmaceuticals usa
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Watson laboratories inc florida
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Jordan VC: Tamoxifen (ICI46,474) as a targeted therapy to treat and prevent breast cancer. Br J Pharmacol. 2006 Jan;147 Suppl 1:S269-76. Pubmed
  2. Jordan VC: Fourteenth Gaddum Memorial Lecture. A current view of tamoxifen for the treatment and prevention of breast cancer. Br J Pharmacol. 1993 Oct;110(2):507-17. Pubmed
  3. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS: Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. Pubmed
  4. Steiner AZ, Terplan M, Paulson RJ: Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis. Hum Reprod. 2005 Jun;20(6):1511-5. Epub 2005 Apr 21. Pubmed
  5. van Bommel EF, Hendriksz TR, Huiskes AW, Zeegers AG: Brief communication: tamoxifen therapy for nonmalignant retroperitoneal fibrosis. Ann Intern Med. 2006 Jan 17;144(2):101-6. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Stilbenes
Substructures
  • Stilbenes
  • Alkanes and Alkenes
  • Phenols and Derivatives
  • Phenylpropenes
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Isoprenes
  • Aromatic compounds
  • Anisoles
  • Styrene Derivatives
  • Phenyl Esters
适应症
药理
Indication For the treatment of breast cancer.
Pharmacodynamics Tamoxifen belongs to a class of drugs called selective estrogen receptor modulators (SERMs), which have both estrogenic and antiestrogenic effects. Tamoxifen has the same nucleus as diethylstilbestrol but possesses an additional side chain (trans isomer) which accounts for its antiestrogenic activity.
Mechanism of action Tamoxifen binds to estrogen receptors (ER), inducing a conformational change in the receptor. This results in a blockage or change in the expression of estrogen dependent genes. The prolonged binding of tamoxifen to the nuclear chromatin of these results in reduced DNA polymerase activity, impaired thymidine utilization, blockade of estradiol uptake, and decreased estrogen response. It is likely that tamoxifen interacts with other coactivators or corepressors in the tissue and binds with different estrogen receptors, ER-alpha or ER-beta, producing both estrogenic and antiestrogenic effects.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Hepatic. Tamoxifen is extensively metabolized after oral administration. N-Desmethyl-tamoxifen is the major metabolite found in plasma. N-Desmethyl-tamoxifen activity is similar to tamoxifen. 4-hydroxy-tamoxifen and a side chain primary alcohol derivative of tamoxifen have been identified as minor metabolites in plasma. 4-Hydroxy-tamoxifen formation is catalyzed mainly by cytochrome P450 (CYP) 2D6, and also by CYP2C9 and 3A4. At high tamoxifen concentrations, CYP2B6 also catalyzes 4-hydroxylation of the parent drug. 4-Hydroxy-tamoxifen possesses 30- to 100-times greater affinity for the estrogen receptor and 30- to 100-times greater potency at inhibiting estrogen-dependent cell proliferation compared to tamoxifen.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Tamoxifen
N-Desmethyltamoxifen Details
Tamoxifen
4-Hydroxytamoxifen Details
Tamoxifen
3-Hydroxytamoxifen (Droloxifene) Details
Tamoxifen
Tamoxifen N-oxide Details
Tamoxifen
4-Hydroxy-N-desmethyl-tamoxifen (endoxifen) Details
Tamoxifen
α-Hydroxy-N-desmethyl-tamoxifen Details
Tamoxifen
N-Didesmethyl-tamoxifen Details
Tamoxifen
3,4-Dihydroxy-tamoxifen Details
Tamoxifen
    		4-hydroxytamoxifen sulfate Details
    Tamoxifen
      		4-hydroxytamoxifen-N-glucuronide Details
      Tamoxifen
        		4-hydroxytamoxifen-O-glucuronide Details
        Tamoxifen
          		Alpha-hydroxy-tamoxifen-O-glucuronide Details
          Tamoxifen
            		Alpha-hydroxytamoxifen Details
            Tamoxifen
              		Endoxifen O-glucuronide Details
              Tamoxifen
                		Endoxifen sulfate Details
                Tamoxifen
                  		Norendoxifen Details
                  Tamoxifen
                    		Tamoxifen-N-glucuronide Details
                    Route of elimination The drug is excreted mainly as polar conjugates, with unchanged drug and unconjugated metabolites accounting for less than 30% of the total fecal radioactivity.
                    Half life Distribution t1/2=7 to 14 hours; Elimination t1/2=5 to 7 days; Elimination t1/2 of N-desmethyl-tamoxifen=9-14 days.
                    Clearance Not Available
                    Toxicity Signs observed at the highest doses following studies to determine LD50 in animals were respiratory difficulties and convulsions.
                    Affected organisms
                    • Humans and other mammals
                    Pathways
                    Pathway Name SMPDB ID
                    Smp00471 Tamoxifen Pathway SMP00471
                    理化性质
                    Properties
                    State solid
                    Experimental Properties
                    Property Value Source
                    melting point 97 °C PhysProp
                    water solubility 0.000167 mg/mL at 25 °C MEYLAN,WM et al. (1996)
                    logP 7.1 Not Available
                    Predicted Properties
                    Property Value Source
                    water solubility 1.02e-03 g/l ALOGPS
                    logP 5.93 ALOGPS
                    logP 6.35 ChemAxon
                    logS -5.6 ALOGPS
                    pKa (strongest basic) 8.76 ChemAxon
                    physiological charge 1 ChemAxon
                    hydrogen acceptor count 2 ChemAxon
                    hydrogen donor count 0 ChemAxon
                    polar surface area 12.47 ChemAxon
                    rotatable bond count 8 ChemAxon
                    refractivity 128.43 ChemAxon
                    polarizability 44.19 ChemAxon
                    药物相互作用
                    Drug Interaction
                    Acenocoumarol Tamoxifen may increase the serum concentration of Acenocoumarol increasing the risk of bleeding. Concomitant therapy should be avoided.
                    Aminoglutethimide Aminoglutethimide may increase Tamoxifen clearance decreasing its therapeutic effect. Consider alternate therapy or monitor for changes in Tamoxifen effects when Aminoglutethimide is initiated, discontinued or dose changed.
                    Amiodarone Amiodarone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Amprenavir Amprenavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Atazanavir Atazanavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Capecitabine Capecitabine may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Capecitabine is initiated, discontinued or dose changed.
                    Chloroquine Chloroquine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Chlorpromazine Chlorpromazine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Cimetidine Cimetidine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Cinacalcet Cinacalcet may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Clarithromycin Clarithromycin may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Clomipramine Clomipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Clozapine Clozapine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Cocaine Cocaine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Conivaptan Conivaptan may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Darifenacin Darifenacin may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Darunavir Darunavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Delavirdine Delavirdine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Desipramine Desipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Diphenhydramine Diphenhydramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Duloxetine Duloxetine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Floxuridine Floxuridine may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Floxiridine is initiated, discontinued or dose changed.
                    Fluconazole Fluconzole may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Fluconazole is initiated, discontinued or dose changed.
                    Fluorouracil Fluorouracil may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Fluorouracil is initiated, discontinued or dose changed.
                    Fluoxetine Fluoxetine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Flurbiprofen Flurbiprofen may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Flurbiprofen is initiated, discontinued or dose changed.
                    Fosamprenavir Fosmprenavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Gemfibrozil Gemfibrozil may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Gemfibrozil is initiated, discontinued or dose changed.
                    Haloperidol Haloperidol may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Ibuprofen Ibuprofen may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Ibuprofen is initiated, discontinued or dose changed.
                    Imatinib Imatinib may increase the serum concentration of Tamoxifen by decreasing its metabolism and clearance. Imatinib may also decrease the therapeutic effect of Tamoxifen by decreasing active metabolite production. Monitor for changes in the therapeutic/adverse effects of Tamoxifen if Imatinib is initiated, discontinued or dose changed.
                    Imipramine Imipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Indinavir Indinavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Indomethacin Indomethacin may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Indomethacin is initiated, discontinued or dose changed.
                    Isoniazid Isoniazid may increase the serum concentration of Tamoxifen by decreasing its metabolism and clearance. Isoniazid may also decrease the therapeutic effect of Tamoxifen by decreasing active metabolite production. Monitor for changes in the therapeutic/adverse effects of Tamoxifen if Isoniazid is initiated, discontinued or dose changed.
                    Itraconazole Itraconazole may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Ketoconazole Ketoconazole may increase the serum concentration of Tamoxifen by decreasing its metabolism and clearance. Ketoconazole may also decrease the therapeutic effect of Tamoxifen by decreasing active metabolite production. Monitor for changes in the therapeutic/adverse effects of Tamoxifen if Ketoconazole is initiated, discontinued or dose changed.
                    Lidocaine Lidocaine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Lopinavir Lopinavir may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Lumefantrine Lumefantrine, a moderate CYP2D6 inhibitor, may decrease the formation of highly potent tamoxifen metabolites. Concomitant therapy may decrease the effectiveness of tamoxifen. Consider alternate therapy.
                    Mefenamic acid Mefenamic acid may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Mefenamic acid is initiated, discontinued or dose changed.
                    Methadone Methadone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Methimazole Methimazole may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Miconazole Miconazole may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Nefazodone Nefazodone may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Nelfinavir Nelfinavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Nicardipine Nicardipine may increase the serum concentration of Tamoxifen by decreasing its metabolism and clearance. Nicardipine may also decrease the therapeutic effect of Tamoxifen by decreasing active metabolite production. Monitor for changes in the therapeutic/adverse effects of Tamoxifen if Nicardipine is initiated, discontinued or dose changed.
                    Nilotinib Nilotinib may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Paroxetine Paroxetine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Pergolide Pergolide may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Pioglitazone Pioglitazone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Piroxicam Piroxicam may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Piroxicam is initiated, discontinued or dose changed.
                    Posaconazole Posaconazole may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Pyrimethamine Pyrimethamine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Quinidine Quinidine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Quinine Quinine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Quinupristin This combination presents an increased risk of toxicity
                    Ranolazine Ranolazine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Rifabutin The rifamycin decreases the effect of anti-estrogen
                    Rifampin The rifamycin decreases the effect of anti-estrogen
                    Ritonavir Ritonavir may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Rivaroxaban Tamoxifen may increase serum concentrations of Rivaroxaban increasing the risk of bleeding. Concomitant therapy should be avoided.
                    Saquinavir Saquinavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
                    Sertraline Sertraline may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Sitaxentan Sitaxsentan may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Sitaxsentan is initiated, discontinued or dose changed.
                    Sulfadiazine Sulfadiazine may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Sulfadiazine is initiated, discontinued or dose changed.
                    Sulfisoxazole Sulfisoxazole may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Sulfisoxazole is initiated, discontinued or dose changed.
                    Telithromycin Telithromycin may reduce clearance of Tamoxifen. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tamoxifen if Telithromycin is initiated, discontinued or dose changed.
                    Terbinafine Terbinafine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
                    Thioridazine Thioridazine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Ticlopidine Ticlopidine may decrease the therapeutic effect of tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tamoxifen. Consider alternate therapy or monitor for changes in Tamoxifen therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
                    Topotecan The p-glycoprotein inhibitor, Tamoxifen, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
                    Tranylcypromine The CYP2D6 inhibitor, Tranylcypromine, may decrease the efficacy of Tamoxifen by reducing active metabolite production. Consider alternate therapy.
                    Trazodone Trazodone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
                    Tretinoin The moderate CYP2C8 inhibitor, Tamoxifen, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Tamoxifen is initiated, discontinued to dose changed.
                    Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of tamoxifen by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of tamoxifen if voriconazole is initiated, discontinued or dose changed.
                    Warfarin Tamoxifen, a CYP2C9 inhibitor, may increase the serum concentration of warfarin by decreasing its metabolism. Concomitant therapy is contraindicated due to significant increase in bleed risk.
                    食物相互作用
                    Not Available

                    返回 | 收藏