Tìm theo
Dexrazoxane
Các tên gọi khác (8 ) :
  • (+)-(S)-4,4'-Propylenedi-2,6-piperazinedione
  • (+)-1,2-Bis(3,5-dioxo-1-piperazinyl)propane
  • 4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione
  • Dexrazoxan
  • Dexrazoxane
  • Dexrazoxano
  • Dexrazoxanum
  • Dextrorazoxane
Thuốc điều trị ung thư
Thuốc Gốc
Small Molecule
CAS: 24584-09-6
ATC: V03AF02
ĐG : Bedford Labs , http://www.bedfordlabs.com
CTHH: C11H16N4O4
PTK: 268.2691
An antimitotic agent with immunosuppressive properties. Dexrazoxane, the (+)-enantiomorph of razoxane, provides cardioprotection against anthracycline toxicity. It appears to inhibit formation of a toxic iron-anthracycline complex. [PubChem] The Food and Drug Administration has designated dexrazoxane as an orphan drug for use in the prevention or reduction in the incidence and severity of anthracycline-induced cardiomyopathy.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C11H16N4O4
Phân tử khối
268.2691
Monoisotopic mass
268.11715502
InChI
InChI=1S/C11H16N4O4/c1-7(15-5-10(18)13-11(19)6-15)2-14-3-8(16)12-9(17)4-14/h7H,2-6H2,1H3,(H,12,16,17)(H,13,18,19)/t7-/m0/s1
InChI Key
InChIKey=BMKDZUISNHGIBY-ZETCQYMHSA-N
IUPAC Name
4-[(2S)-1-(3,5-dioxopiperazin-1-yl)propan-2-yl]piperazine-2,6-dione
Traditional IUPAC Name
4-[(2S)-1-(3,5-dioxopiperazin-1-yl)propan-2-yl]piperazine-2,6-dione
SMILES
C[C@@H](CN1CC(=O)NC(=O)C1)N1CC(=O)NC(=O)C1
Độ tan chảy
191-197 °C
Độ hòa tan
Sparingly soluble
logP
-2.6
logS
-1.4
pKa (strongest acidic)
11.2
pKa (Strongest Basic)
3.6
PSA
98.82 Å2
Refractivity
64.25 m3·mol-1
Polarizability
26.12 Å3
Rotatable Bond Count
3
H Bond Acceptor Count
6
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
2
Bioavailability
1
Rule of Five
true
pKa
2.1
Dược Lực Học : Dexrazoxane is a cardioprotective agent for use in conjunction with doxorubicin indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose. Patients receiving anthracycline-derivative antineoplastic agents may experience three types of cardiotoxicity: acute transient type; chronic, subacute type (related to cumulative dose and has a more indolent onset later on); and a late-onset type that manifests years after therapy, mainly in patients that have been exposed to the drug as a child. Although the exact mechanism of anthracycline-induced cardiotoxicity is not known, it has shown to exert a variety of actions that may result in the development of cardiotoxicity. In animals, anthracyclines cause a selective inhibition of cardiac muscle gene expression for α-actin, troponin, myosin light-chain 2, and the M isoform of creatine kinase. This may lead to myofibrillar loss associated with anthracycline-induced cardiotoxicity. Anthracyclines may also cause myocyte damage via calcium overload, altered myocardial adrenergic function, release of vasoactive amines, and proinflammatory cytokines. Furthermore, it has been suggested that the main cause of anthracycline-induced cardiotoxicity is associated with free-radical damage to DNA. The drugs intercalate DNA, chelate metal ions to produce drug-metal complexes, and generate superoxide radicals via oxidation-reduction reactions. Anthracyclines also contain a quinone structure that can undergo reduction via NADPH-dependent reactions to produce a semiquinone free radical that initiates a cascade of superoxide and hydroxide radical generation. Chelation of metal ions, particularly iron, by anthracyclines results in an anthracycline-metal complex that catalyzes the generation of reactive oxygen free radicals. This complex is a powerful oxidant that can initiate lipid peroxidation in the absence of oxygen free radicals. The toxicity induced by antrhacyclines may be exacerbated in cardiac cells, as these cells do not possess sufficient amounts of certain enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) involved in detoxifying free radicals and protecting the cells from subsequent damage.
Cơ Chế Tác Dụng : An antimitotic agent with immunosuppressive properties. Dexrazoxane, the (+)-enantiomorph of razoxane, provides cardioprotection against anthracycline toxicity. It appears to inhibit formation of a toxic iron-anthracycline complex. [PubChem] The Food and Drug Administration has designated dexrazoxane as an orphan drug for use in the prevention or reduction in the incidence and severity of anthracycline-induced cardiomyopathy. The mechanism by which dexrazoxane exerts its cardioprotective activity is not fully understood. Dexrazoxane is a cyclic derivative of EDTA that readily penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane (a prodrug) is converted intracellularly to a ring-opened bidentate chelating agent that chelates to free iron and interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy. It should be noted that dexrazoxane may also be protective through its inhibitory effect on topoisomerase II.
Dược Động Học :
▧ Absorption :
IV administration results in complete bioavailability.
▧ Volume of Distribution :
* 9 to 22.6 L/m^2
▧ Protein binding :
Very low (< 2%)
▧ Metabolism :
Dexrazoxane is hydrolysed by the enzyme dihydropyrimidine amidohydrolase in the liver and kidney to active metabolites that are capable of binding to metal ions.
▧ Route of Elimination :
Urinary excretion plays an important role in the elimination of dexrazoxane. Forty-two percent of the 500 mg/m2 dose of dexrazoxane was excreted in the urine.
▧ Half Life :
2.5 hours
▧ Clearance :
* 7.88 L/h/m2 [dose of 50 mg/m2 Doxorubicin and 500 mg/m2 Dexrazoxane] * 6.25 L/h/m2 [dose of 60 mg/m2 Doxorubicin and 600 mg/m2 Dexrazoxane]
Độc Tính : Intraperitoneal, mouse LD10 = 500 mg/kg. Intravenous, dog LD10 = 2 gm/kg.
Chỉ Định : For reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m^2 and would benefit from continued doxorubicin therapy. Also approved for the treatment of extravasation from intravenous anthracyclines.
Liều Lượng & Cách Dùng : Powder, for solution - Intravenous
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Dexrazoxane 250 mg vial
    Giá bán buôn : USD >246.28
    Đơn vị tính : vial
  • Biệt dược thương mại : Zinecard 250 mg vial
    Giá bán buôn : USD >258.59
    Đơn vị tính : vial
  • Biệt dược thương mại : Dexrazoxane 500 mg vial
    Giá bán buôn : USD >492.55
    Đơn vị tính : vial
  • Biệt dược thương mại : Zinecard 500 mg vial
    Giá bán buôn : USD >517.18
    Đơn vị tính : vial
Nhà Sản Xuất
  • Sản phẩm biệt dược : Ao Nuo Xian
  • Công ty : Novartis
    Sản phẩm biệt dược : Cardioxane
  • Công ty : Raffo
    Sản phẩm biệt dược : Dexrazoxane
  • Công ty : TopoTarget
    Sản phẩm biệt dược : Savene
  • Công ty : TopoTarget
    Sản phẩm biệt dược : Totect
  • Công ty : Pfizer
    Sản phẩm biệt dược : Zinecard
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00380
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=71384
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505982
ChemSpider
http://www.chemspider.com/Chemical-Structure.64479.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/38423-110-01
PharmGKB
http://www.pharmgkb.org/drug/PA449259
Wikipedia
http://en.wikipedia.org/wiki/Dexrazoxane
RxList
http://www.rxlist.com/cgi/generic2/dexrazoxane.htm
Drugs.com
http://www.drugs.com/cdi/dexrazoxane.html
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