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Statements

Subject Item
n2:DB00675
rdf:type
n3:Drug
n3:description
One of the selective estrogen receptor modulators (SERM) with tissue-specific activities for the treatment and prevention of estrogen receptor positive breast cancer. 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]
n3:dosage
n16:271B41F1-363D-11E5-9242-09173F13E4C5 n16:271B41F2-363D-11E5-9242-09173F13E4C5 n16:271B41F3-363D-11E5-9242-09173F13E4C5 n16:271B41F4-363D-11E5-9242-09173F13E4C5 n16:271B41F5-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# 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":http://www.ncbi.nlm.nih.gov/pubmed/16402113 # 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":http://www.ncbi.nlm.nih.gov/pubmed/8242225 # 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":http://www.ncbi.nlm.nih.gov/pubmed/15639680 # 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":http://www.ncbi.nlm.nih.gov/pubmed/15845599 # 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":http://www.ncbi.nlm.nih.gov/pubmed/16418409 # FDA label
n3:group
approved
n3:halfLife
The decline in tamoxifen plasma concentrations is biphasic with a terminal elimination half-life of approximately 5 to 7 days. The estimated half-life of N-desmethyl tamoxifen is 14 days.
n3:indication
Tamoxifen is indicated for the treatment of metastatic breast cancer in women and men and ductal carcinoma in Situ.
n3:manufacturer
n10:271B41E8-363D-11E5-9242-09173F13E4C5 n10:271B41E9-363D-11E5-9242-09173F13E4C5 n10:271B41E6-363D-11E5-9242-09173F13E4C5 n10:271B41E7-363D-11E5-9242-09173F13E4C5 n10:271B41E4-363D-11E5-9242-09173F13E4C5 n10:271B41E5-363D-11E5-9242-09173F13E4C5 n10:271B41E2-363D-11E5-9242-09173F13E4C5 n10:271B41E3-363D-11E5-9242-09173F13E4C5 n10:271B41E0-363D-11E5-9242-09173F13E4C5 n10:271B41E1-363D-11E5-9242-09173F13E4C5 n10:271B41DF-363D-11E5-9242-09173F13E4C5
owl:sameAs
n33:DB00675 n35:DB00675
dcterms:title
Tamoxifen
adms:identifier
n9:2733526 n11:46505515 n12:OHT n13:PA451581 n18:20607 n19:9396 n20:Tamoxifen n21:D00966 n22:0378-0144-91 n23:1016 n24:C07108 n25:1016 n26:2015313 n27:DB00675
n3:mechanismOfAction
Tamoxifen is a nonsteroidal agent that 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.
n3:packager
n10:271B41DE-363D-11E5-9242-09173F13E4C5 n10:271B41DC-363D-11E5-9242-09173F13E4C5 n10:271B41D5-363D-11E5-9242-09173F13E4C5 n10:271B41DD-363D-11E5-9242-09173F13E4C5 n10:271B41D7-363D-11E5-9242-09173F13E4C5 n10:271B41DA-363D-11E5-9242-09173F13E4C5 n10:271B41DB-363D-11E5-9242-09173F13E4C5 n10:271B41D8-363D-11E5-9242-09173F13E4C5 n10:271B41D9-363D-11E5-9242-09173F13E4C5 n10:271B41D2-363D-11E5-9242-09173F13E4C5 n10:271B41D3-363D-11E5-9242-09173F13E4C5 n10:271B41D0-363D-11E5-9242-09173F13E4C5 n10:271B41D1-363D-11E5-9242-09173F13E4C5 n10:271B41D4-363D-11E5-9242-09173F13E4C5 n10:271B41CA-363D-11E5-9242-09173F13E4C5 n10:271B41CB-363D-11E5-9242-09173F13E4C5 n10:271B41C8-363D-11E5-9242-09173F13E4C5 n10:271B41C9-363D-11E5-9242-09173F13E4C5 n10:271B41CE-363D-11E5-9242-09173F13E4C5 n10:271B41CF-363D-11E5-9242-09173F13E4C5 n10:271B41CC-363D-11E5-9242-09173F13E4C5 n10:271B41CD-363D-11E5-9242-09173F13E4C5 n10:271B41C6-363D-11E5-9242-09173F13E4C5 n10:271B41C7-363D-11E5-9242-09173F13E4C5 n10:271B41D6-363D-11E5-9242-09173F13E4C5
n3:patent
n4:6127425
n3:routeOfElimination
65% of the dose was excreted from the body over 2 weeks in which fecal excretion was the primary route of elimination. Tamoxifen is excreted mainly as polar conjugates, with unchanged drug and unconjugated metabolites accounting for less than 30% of the total fecal radioactivity.
n3:synonym
Tamone Noltam Citofen Nourytam Istubol (Z)-2-(4-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylethanamine Tamoxifeno Valodex Apo-tamox Tamoxifene 1-P-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene 1-Para-beta-dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene Zemide Diemon (Z)-2-(Para-(1,2-diphenyl-1-butenyl)phenoxy)-N,N-dimethylamine Tamofen Tamoxifenum Retaxim Gen-tamoxifen Crisafeno Tamoxasta trans-Tamoxifen Oncomox Tamoxifen Tamoxifène
n3:toxicity
Signs observed at the highest doses following studies to determine LD<sub>50</sub> in animals were respiratory difficulties and convulsions.
n14:hasAHFSCode
n15:10-00-00
n3:salt
n3:synthesisReference
Chengjian Mao, "Tamoxifen and 4-hydroxytamoxifen-activated system for regulated production of proteins in eukaryotic cells." U.S. Patent US20030199022, issued October 23, 2003.
n30:hasConcept
n31:M0021024
foaf:page
n6:tamox.htm n34:tamoxifen.html
n3:IUPAC-Name
n7:271B41FA-363D-11E5-9242-09173F13E4C5
n3:InChI
n7:271B4200-363D-11E5-9242-09173F13E4C5
n3:Molecular-Formula
n7:271B41FF-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n7:271B41FC-363D-11E5-9242-09173F13E4C5
n3:Monoisotopic-Weight
n7:271B41FD-363D-11E5-9242-09173F13E4C5
n3:SMILES
n7:271B41FE-363D-11E5-9242-09173F13E4C5
n3:Water-Solubility
n7:271B420F-363D-11E5-9242-09173F13E4C5 n7:271B41F8-363D-11E5-9242-09173F13E4C5
n3:logP
n7:271B4211-363D-11E5-9242-09173F13E4C5 n7:271B41F6-363D-11E5-9242-09173F13E4C5 n7:271B41F9-363D-11E5-9242-09173F13E4C5
n3:logS
n7:271B41F7-363D-11E5-9242-09173F13E4C5
n14:hasATCCode
n29:L02BA01
n3:H-Bond-Acceptor-Count
n7:271B4206-363D-11E5-9242-09173F13E4C5
n3:H-Bond-Donor-Count
n7:271B4207-363D-11E5-9242-09173F13E4C5
n3:InChIKey
n7:271B4201-363D-11E5-9242-09173F13E4C5
n3:Polar-Surface-Area--PSA-
n7:271B4202-363D-11E5-9242-09173F13E4C5
n3:Polarizability
n7:271B4204-363D-11E5-9242-09173F13E4C5
n3:Refractivity
n7:271B4203-363D-11E5-9242-09173F13E4C5
n3:Rotatable-Bond-Count
n7:271B4205-363D-11E5-9242-09173F13E4C5
n3:absorption
When a single oral dose of 20 mg is given, the average peak plasma concentration (Cmax) is 40 ng/mL which occurred approximately 5 hours after dosing (Tmax). The Cmax of N-desmethyl tamoxifen is 15 ng/mL. Steady-state concentrations for tamoxifen is achieved in 4 weeks, while steady-state concentrations for N-desmethyl tamoxifen is achieved in 8 weeks.
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
10540-29-1
n3:category
n3:clearance
Clearance (CL/F) as body weight adjusted in female pediatric patients was approximately 2.3-fold higher than in female breast cancer patients.
n3:containedIn
n28:271B41EF-363D-11E5-9242-09173F13E4C5 n28:271B41F0-363D-11E5-9242-09173F13E4C5 n28:271B41EA-363D-11E5-9242-09173F13E4C5 n28:271B41EB-363D-11E5-9242-09173F13E4C5 n28:271B41EC-363D-11E5-9242-09173F13E4C5 n28:271B41ED-363D-11E5-9242-09173F13E4C5 n28:271B41EE-363D-11E5-9242-09173F13E4C5
n3:Bioavailability
n7:271B420B-363D-11E5-9242-09173F13E4C5
n3:Ghose-Filter
n7:271B420D-363D-11E5-9242-09173F13E4C5
n3:MDDR-Like-Rule
n7:271B420E-363D-11E5-9242-09173F13E4C5
n3:Melting-Point
n7:271B4210-363D-11E5-9242-09173F13E4C5
n3:Number-of-Rings
n7:271B420A-363D-11E5-9242-09173F13E4C5
n3:Physiological-Charge
n7:271B4209-363D-11E5-9242-09173F13E4C5
n3:Rule-of-Five
n7:271B420C-363D-11E5-9242-09173F13E4C5
n3:Traditional-IUPAC-Name
n7:271B41FB-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-basic-
n7:271B4208-363D-11E5-9242-09173F13E4C5