Tìm theo
Mifepristone
Các tên gọi khác (10 ) :
  • 11-(4-DIMETHYLAMINO-phenyl)-17-hydroxy-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,13,14,15,16,17-dodec ahydro-cyclopenta[a]phenanthren-3-one
  • Corlux
  • Mifegyne
  • Mifeprex
  • Mifepriston
  • Mifepristona
  • Mifépristone
  • Mifepristonum
  • RU-486
  • RU486
Hormon, Nội tiết tố
Thuốc Gốc
Small Molecule
CAS: 84371-65-3
ATC: G03XB01
ĐG : Danco Labs LLC
CTHH: C29H35NO2
PTK: 429.5937
A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary cushing syndrome [PubChem]. The two marketed forms of mifepristone are Mifeprex® (mifepristone 200mg) and Korlym™ (mifepristone 300mg). Currently under investigation for use in psychotic depression (phase 3 trials).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C29H35NO2
Phân tử khối
429.5937
Monoisotopic mass
429.266779369
InChI
InChI=1S/C29H35NO2/c1-5-15-29(32)16-14-26-24-12-8-20-17-22(31)11-13-23(20)27(24)25(18-28(26,29)2)19-6-9-21(10-7-19)30(3)4/h6-7,9-10,17,24-26,32H,8,11-14,16,18H2,1-4H3/t24-,25+,26-,28-,29-/m0/s1
InChI Key
InChIKey=VKHAHZOOUSRJNA-GCNJZUOMSA-N
IUPAC Name
(10S,11S,14S,15S,17R)-17-[4-(dimethylamino)phenyl]-14-hydroxy-15-methyl-14-(prop-1-yn-1-yl)tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-1,6-dien-5-one
Traditional IUPAC Name
mifepristone
SMILES
[H][C@@]12CC[C@@](O)(C#CC)[C@@]1(C)C[C@H](C1=CC=C(C=C1)N(C)C)C1=C3CCC(=O)C=C3CC[C@@]21[H]
Độ tan chảy
191-196 °C
Độ hòa tan
Poorly soluble
logP
4.5
logS
-5.1
pKa (strongest acidic)
12.87
pKa (Strongest Basic)
4.89
PSA
40.54 Å2
Refractivity
132.58 m3·mol-1
Polarizability
50.71 Å3
Rotatable Bond Count
3
H Bond Acceptor Count
3
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
5
Bioavailability
1
Dược Lực Học : Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol.
Cơ Chế Tác Dụng : A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary cushing syndrome [PubChem]. The two marketed forms of mifepristone are Mifeprex® (mifepristone 200mg) and Korlym™ (mifepristone 300mg). Currently under investigation for use in psychotic depression (phase 3 trials). The anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results. In the treatment of Cushing's syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels.
Dược Động Học :
▧ Absorption :
The absolute bioavailability of a 20 mg oral dose is 69%
▧ Protein binding :
98% (bound to plasma proteins, albumin and a 1-acid glycoprotein)
▧ Metabolism :
Hepatic. Hepatic, by Cytochrome P450 3A4 isoenzyme to the N-monodemethylated metabolite (RU 42 633); RU 42 698, which results from the loss of two methyl groups from position 11 beta; and RU 42 698, which results from terminal hydroxylation of the 17–propynyl chain.
▧ Route of Elimination :
Fecal: 83%; Renal: 9%.
▧ Half Life :
18 hours
Độc Tính : Nearly all of the women who receive mifepristone will report adverse reactions, and many can be expected to report more than one such reaction. About 90% of patients report adverse reactions following administration of misoprostol on day three of the treatment procedure. Side effects include more heavy bleeding than a heavy menstrual period, abdominal pain, uterine cramping, nausea, vomiting, and diarrhea.
Chỉ Định : For the medical termination of intrauterine pregnancy through 49 days' pregnancy. Also indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and are not candidates for surgery or have had unsuccessful surgery.
Tương Tác Thuốc :
  • Buserelin Buserelin moderately contributes to Q-Tc prolongation. Combination must be avoided because mifepristone can further enhance that effect.
  • Dabigatran etexilate May lead to excessive post-abortion bleeding in patients on anticoagulant therapy. Concomitant therapy is contraindicated.
  • Degarelix Enhance QTc-prolonging effect
  • Etravirine Mifepristone, when used concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to avoid concurrent therapy.
  • Oxytocin Consider therapy modification because of potential enhanced effect of Q-Tc prolongation
  • Pasireotide Avoid combination with mifepristone and other moderate to high risk QTc prolonging agents. The combinaton may enhance the QTc-prolonging effect of these drugs.
  • Tofacitinib Mifepristone, when used in combination with tofacitinib, may increase tofacitinib concentrations. It is recommended to adjust therapy by using a minimized dose of tofacitinib, and monitoring for increased tofacitinib concentrations and signs of toxicity, during and 2 weeks after discontinuation of mifepristone therapy.
Liều Lượng & Cách Dùng : Tablet - Oral - 200mg
Tablet - Oral - 300mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Mifeprex 200 mg tablet
    Giá bán buôn : USD >90.0
    Đơn vị tính : tablet
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00834
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=55245
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505795
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07652
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00585
ChemSpider
http://www.chemspider.com/Chemical-Structure.49889.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=18627
PharmGKB
http://www.pharmgkb.org/drug/PA450500
Wikipedia
http://en.wikipedia.org/wiki/Mifepristone
RxList
http://www.rxlist.com/cgi/generic3/mifeprist.htm
Drugs.com
http://www.drugs.com/cdi/mifepristone.html
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