Tìm theo
Doxorubicin
Các tên gọi khác (9 ) :
  • (1S,3S)-3-Glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranoside
  • (8S-cis)-10-((3-amino-2,3,6-Trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione
  • 14-hydroxydaunomycin
  • 14-hydroxydaunorubicine
  • Adriamycin
  • Doxorubicin
  • Doxorubicine
  • Doxorubicinum
  • Hydroxydaunorubicin
Thuốc chống ung thư và tác động vào hệ thống miễn dịch
Thuốc Gốc
Small Molecule
CAS: 23214-92-8
ATC: L01DB01
ĐG : Alza Corp.
CTHH: C27H29NO11
PTK: 543.5193
Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius. Doxorubicin binds to nucleic acids, presumably by specific intercalation of the planar anthracycline nucleus with the DNA double helix.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C27H29NO11
Phân tử khối
543.5193
Monoisotopic mass
543.174060775
InChI
InChI=1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,17-,22+,27-/m0/s1
InChI Key
InChIKey=AOJJSUZBOXZQNB-TZSSRYMLSA-N
IUPAC Name
(8S,10S)-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione
Traditional IUPAC Name
doxorubicin
SMILES
COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O
Độ tan chảy
229-231 °C
Độ hòa tan
Soluble
logP
1.27
logS
-2.7
pKa (strongest acidic)
9.53
pKa (Strongest Basic)
8.94
PSA
206.07 Å2
Refractivity
134.59 m3·mol-1
Polarizability
53.87 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
12
H Bond Donor Count
6
Physiological Charge
1
Number of Rings
5
Bioavailability
0
caco2 Permeability
-6.8
Dược Lực Học : Doxorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Doxorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Doxorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.
Cơ Chế Tác Dụng : Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius. Doxorubicin binds to nucleic acids, presumably by specific intercalation of the planar anthracycline nucleus with the DNA double helix. Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.
Dược Động Học :

▧ Volume of Distribution :
The distributive half-life is 5 minutes, which suggests that doxorubicin is rapidly taken up by tissue. Steady state volume of distribution = 809 to 1214 L/m2
▧ Protein binding :
Doxorubicin and its major metabolite, doxorubicinol, is 74-76% bound to plasma protein. The extent to binding is independent of plasma concentration up to 1.1 mcg/mL. Doxorubicin does not cross the blood brain barrier.
▧ Metabolism :
Doxorubicin is capable of undergoing 3 metabolic routes: one-electron reduction, two-electron reduction, and deglycosidation. However, approximately half of the dose is eliminated from the body unchanged. Two electron reduction yields doxorubicinol, a secondary alcohol. This pathway is considered the primary metabolic pathway. The one electron reduction is facilitated by several oxidoreductases to form a doxirubicin-semiquinone radical. These enzymes include mitochondrial and cystolic NADPH dehydrogenates, xanthine oxidase, and nitric oxide synthases. Deglycosidation is a minor metabolic pathway (1-2% of the dose undergoes this pathway). The resultant metabolites are deoxyaglycone or hydroxyaglycone formed via reduction or hydrolysis respectively. Enzymes that may be involved with this pathway include xanthine oxidase, NADPH-cytochrome P450 reductase, and cytosolic NADPH dehydrogenase.
▧ Route of Elimination :
40% of the dose appears in bile in 5 days. 5-12% of the drug and its metabolites appears in urine during the same time period. <3% of the dose recovered in urine was doxorubicinol.
▧ Half Life :
Terminal half life = 20 - 48 hours.
▧ Clearance :
* 324-809 mL/min/m2 [by metabolism and biliary excretion] * 1088 mL/min/m2 [Men] * 433 mL/min/m2 [Women] * 1540 mL/min/m2 [children greater than 2 years of age receiving administration of 10 to 75 mg/m2 doses] * 813 mL/min/m2 [infants younger than 2 years of age receiving administration of 10 to 75 mg/m2 doses]
Độc Tính : LD50=21800 ug/kg (rat, subcutaneous)
Chỉ Định : Doxorubicin is used to produce regression in disseminated neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms’ tumor, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin’s disease, malignant lymphoma and bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types. Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer.
Tương Tác Thuốc :
  • Dabigatran etexilate P-Glycoprotein inducers such as doxorubicin may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
  • Digoxin The antineoplasic agent decreases the effect of digoxin
  • Telithromycin Telithromycin may reduce clearance of Doxorubicin. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Doxorubicin if Telithromycin is initiated, discontinued or dose changed.
  • Terbinafine Terbinafine may reduce the metabolism and clearance of Doxorubicin. Consider alternate therapy or monitor for therapeutic/adverse effects of Doxorubicin if Terbinafine is initiated, discontinued or dose changed.
  • Trastuzumab Trastuzumab may increase the cardiotoxicity of Doxorubicin. Signs and symptoms of cardiac dysfunction should be monitored for frequently. Increased risk of heart failure. Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of doxorubicin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxorubicin if voriconazole is initiated, discontinued or dose changed.
  • Zidovudine Additive myelosuppression may occur. Doxorubicin may decrease the efficacy of zidovudine. Concomitant therapy should be avoided.
Liều Lượng & Cách Dùng : Injection, powder, for solution - Intravenous - 10 mg, 20 mg, 50 mg
Injection, solution - Intravenous - 2 mg/mL
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Adriamycin 10 mg vial
    Giá bán buôn : USD >13.2
    Đơn vị tính : vial
  • Biệt dược thương mại : Adriamycin 20 mg vial
    Giá bán buôn : USD >26.4
    Đơn vị tính : vial
  • Biệt dược thương mại : Doxorubicin 10 mg vial
    Giá bán buôn : USD >44.4
    Đơn vị tính : vial
  • Biệt dược thương mại : Adriamycin 50 mg vial
    Giá bán buôn : USD >64.8
    Đơn vị tính : vial
  • Biệt dược thương mại : Doxil 2 mg/ml vial
    Giá bán buôn : USD >115.78
    Đơn vị tính : ml
  • Biệt dược thương mại : Doxorubicin 50 mg vial
    Giá bán buôn : USD >132.0
    Đơn vị tính : vial
Nhà Sản Xuất
  • Công ty : Pfizer
    Sản phẩm biệt dược : Adriablastina
  • Công ty : Pfizer
    Sản phẩm biệt dược : Adriamycin
  • Công ty : Actavis
    Sản phẩm biệt dược : Adriblastin
  • Công ty : Janssen-Cilag
    Sản phẩm biệt dược : Caelyx
  • Công ty : Janssen
    Sản phẩm biệt dược : Doxil
  • Công ty : Cephalon
    Sản phẩm biệt dược : Myocet
  • Công ty :
    Sản phẩm biệt dược : Rubex
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00997
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=31703
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507641
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C01661
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D03899
ChemSpider
http://www.chemspider.com/Chemical-Structure.29400.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=22984
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0703-5043-03
PharmGKB
http://www.pharmgkb.org/drug/PA449412
Wikipedia
http://en.wikipedia.org/wiki/Doxorubicin
RxList
http://www.rxlist.com/cgi/generic2/doxor.htm
Drugs.com
http://www.drugs.com/cdi/doxorubicin.html
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