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药品详细

Aminoglutethimide(氨鲁米特)

化学结构式图
中文名
氨鲁米特
英文名
Aminoglutethimide
分子式
C13H16N2O2
化学名
3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione
分子量
Average: 232.2783
Monoisotopic: 232.121177766
CAS号
125-84-8
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

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)

生产厂家
  • Novartis pharmaceuticals corp
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes
  • Delta Lactams
  • Phenylpiperidines
Substructures
  • Carbonyl Compounds
  • Delta Lactams
  • Carboxylic Acids and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Phenylpiperidines
  • Piperidines
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Anilines
适应症
药理
Indication 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.
Pharmacodynamics Aminoglutethimide inhibits the enzymatic conversion of cholesterol to D5-pregnenolone, resulting in a decrease in the production of adrenal glucocorticoids, mineralocorticoids, estrogens, and androgens.
Mechanism of action 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.
Absorption Rapidly and completely absorbed from gastrointestinal tract. The bioavailability of tablets is equivalent to equal doses given as a solution.
Volume of distribution Not Available
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
Clearance Not Available
Toxicity 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.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 149.5 °C PhysProp
water solubility Practically insoluble in water Not Available
logP 1.3 Not Available
Predicted Properties
Property Value Source
water solubility 3.71e-01 g/l ALOGPS
logP 1.49 ALOGPS
logP 1.3 ChemAxon
logS -2.8 ALOGPS
pKa (strongest acidic) 11.69 ChemAxon
pKa (strongest basic) 4.28 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 72.19 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 65.35 ChemAxon
polarizability 24.69 ChemAxon
药物相互作用
Drug Interaction
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.
Dicumarol 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.
食物相互作用
  • Take without regard to meals.

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