Aminoglutethimide

Các tên gọi khác (12 ) :

2-(p-Aminophenyl)-2-ethylglutarimide
3-Ethyl-3-(P-aminophenyl)-2,6-dioxopiperidine
alpha-(P-Aminophenyl)-alpha-ethylglutarimide
Aminoglutethimid
Aminoglutéthimide
Aminoglutethimide
Aminoglutethimidum
Aminoglutetimida
Aminoglutetimide
Dl-Aminoglutethimide
Elipten
P-Aminoglutethimide

Thuốc điều trị ung thư

Thuốc Gốc

Small Molecule

CAS: 125-84-8

ATC: L02BG01

ĐG : Kaiser Foundation Hospital

CTHH: C₁₃H₁₆N₂O₂

PTK: 232.2783

An aromatase inhibitor that produces a state of "medical" adrenalectomy by blocking the production of adrenal steroids. It also blocks the conversion of androgens to estrogens. Aminoglutethimide has been used in the treatment of advanced breast and prostate cancer. It was formerly used for its weak anticonvulsant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p454)

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₁₃H₁₆N₂O₂

Phân tử khối

232.2783

Monoisotopic mass

232.121177766

InChI

InChI=1S/C13H16N2O2/c1-2-13(8-7-11(16)15-12(13)17)9-3-5-10(14)6-4-9/h3-6H,2,7-8,14H2,1H3,(H,15,16,17)

InChI Key

InChIKey=ROBVIMPUHSLWNV-UHFFFAOYSA-N

IUPAC Name

3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione

Traditional IUPAC Name

aminoglutethimide

SMILES

CCC1(CCC(=O)NC1=O)C1=CC=C(N)C=C1

Độ tan chảy

223-225

Độ hòa tan

Practically insoluble in water

logP

1.3

logS

-2.8

pKa (strongest acidic)

11.69

pKa (Strongest Basic)

4.28

PSA

72.19 Å²

Refractivity

65.35 m³·mol^-1

Polarizability

24.69 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Rule of Five

true

Ghose Filter

true

Dược Lực Học : Aminoglutethimide inhibits the enzymatic conversion of cholesterol to D5-pregnenolone, resulting in a decrease in the production of adrenal glucocorticoids, mineralocorticoids, estrogens, and androgens.

Cơ Chế Tác Dụng : An aromatase inhibitor that produces a state of "medical" adrenalectomy by blocking the production of adrenal steroids. It also blocks the conversion of androgens to estrogens. Aminoglutethimide has been used in the treatment of advanced breast and prostate cancer. It was formerly used for its weak anticonvulsant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p454) Aminoglutethimide reduces the production of D5-pregnenolone and blocks several other steps in steroid synthesis, including the C-11, C-18, and C-21 hydroxylations and the hydroxylations required for the aromatization of androgens to estrogens, mediated through the binding of aminoglutethimide to cytochrome P-450 complexes. Specifically, the drug binds to and inhibits aromatase which is essential for the generation of estrogens from androstenedione and testosterone. A decrease in adrenal secretion of cortisol is followed by an increased secretion of pituitary adrenocorticotropic hormone (ACTH), which will overcome the blockade of adrenocortical steroid synthesis by aminoglutethimide. The compensatory increase in ACTH secretion can be suppressed by the simultaneous administration of hydrocortisone. Since aminoglutethimide increases the rate of metabolism of dexamethasone but not that of hydrocortisone, the latter is preferred as the adrenal glucocorticoid replacement. Although aminoglutethimide inhibits the synthesis of thyroxine by the thyroid gland, the compensatory increase in thyroid-stimulating hormone (TSH) is frequently of sufficient magnitude to overcome the inhibition of thyroid synthesis due to aminoglutethimide. In spite of an increase in TSH, aminoglutethimide has not been associated with increased prolactin secretion.

Dược Động Học :

▧ Absorption :
Rapidly and completely absorbed from gastrointestinal tract. The bioavailability of tablets is equivalent to equal doses given as a solution.
▧ Protein binding :
21-25%
▧ Metabolism :
Hepatic. 34-54% of the administered dose is excreted in the urine as unchanged drug during the first 48 hours, and an additional fraction as an N-acetyl derivative.
▧ Route of Elimination :
After ingestion of a single oral dose, 34%-54% is excreted in the urine as unchanged drug during the first 48 hours, and an additional fraction as the N-acetyl derivative.
▧ Half Life :
12.5 ± 1.6 hours

Độc Tính : Oral LD50s (mg/kg): rats, 1800; dogs, >100. Intravenous LD50s (mg/kg): rats, 156; dogs, >100. Symptoms of overdose include respiratory depression, hypoventilation, hypotension, hypovolemic shock due to dehydration, somnolence, lethargy, coma, ataxia, dizziness, fatigue, nausea, and vomiting.

Chỉ Định : For the suppression of adrenal function in selected patients with Cushing's syndrome, malignant neoplasm of the female breast, and carcinoma in situ of the breast.

Tương Tác Thuốc :

Acenocoumarol Aminoglutethimide may decrease the anticoagulant effect of acenocoumarol.
Anisindione Aminoglutethimide may decrease the anticoagulant effect of anisindione.
Dexamethasone Aminoglutethimide may decrease the effect of dexamethasone.
Dicoumarol Aminoglutethimide may decrease the anticoagulant effect of dicumarol.
Tamoxifen 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.
Telithromycin Aminoglutethimide may decrease the plasma concentration of Telithromycin. Consider alternate therapy.
Temsirolimus Aminoglutethimide may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Tramadol Aminoglutethimide may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inducer, Aminoglutethimide, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Aminoglutethimide is initiated, discontinued or dose changed.
Warfarin Aminoglutethimide may decrease the anticoagulant effect of warfarin by increasing its metabolism. Monitor for changes in prothrombin time and therapeutic effects of warfarin if aminoglutethimide is initiated, discontinued or dose changed.

Liều Lượng & Cách Dùng : Tablet - Oral - 250 mg

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : Novartis

Sản phẩm biệt dược : Cytadren
Công ty : Pliva Hrvatska

Sản phẩm biệt dược : Mamomit
Công ty : Novartis

Sản phẩm biệt dược : Orimeten
Công ty : Actavis

Sản phẩm biệt dược : Rogluten

Đóng gói

Công ty : Kaiser Foundation Hospital
Công ty : Novartis AG

Website : http://www.novartis.com
Công ty : Patheon Inc.

Website : http://www.patheon.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB00357

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2145

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506066

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C07617

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D00574

ChemSpider

http://www.chemspider.com/Chemical-Structure.2060.html

BindingDB

http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=9460

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0083-0024-30

PharmGKB

http://www.pharmgkb.org/drug/PA448375

Wikipedia

http://en.wikipedia.org/wiki/Aminoglutethimide

RxList

http://www.rxlist.com/cgi/generic3/cytadren.htm

Drugs.com

http://www.drugs.com/cdi/aminoglutethimide.html

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