Tìm theo
Cyclophosphamide
Các tên gọi khác (13 ) :
  • (+-)-Cyclophosphamide
  • (RS)-Cyclophosphamide
  • 2-[Bis(2-chloroethylamino)]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide
  • Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester
  • Ciclofosfamida
  • Ciclofosfamide
  • Cyclophosphamid
  • Cyclophosphamide
  • Cyclophosphamide anhydrous
  • Cyclophosphamidum
  • Cytophosphane
  • Ledoxina
  • N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide
Thuốc chống ung thư và tác động vào hệ thống miễn dịch
Thuốc Gốc
Small Molecule
CAS: 50-18-0
ATC: L01AA01, L01DB07
ĐG : Baxter International Inc. , http://www.baxter.com
CTHH: C7H15Cl2N2O2P
PTK: 261.086
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C7H15Cl2N2O2P
Phân tử khối
261.086
Monoisotopic mass
260.02481966
InChI
InChI=1S/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12)
InChI Key
InChIKey=CMSMOCZEIVJLDB-UHFFFAOYSA-N
IUPAC Name
2-[bis(2-chloroethyl)amino]-1,3,2$l^{5}-oxazaphosphinan-2-one
Traditional IUPAC Name
cyclophosphamide
SMILES
ClCCN(CCCl)P1(=O)NCCCO1
Độ tan chảy
48-49
Độ hòa tan
Soluble. 1-5 g/100 mL at 23 °C
logP
0.8
logS
-1.2
pKa (strongest acidic)
12.78
pKa (Strongest Basic)
-0.57
PSA
41.57 Å2
Refractivity
58.48 m3·mol-1
Polarizability
23.72 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
2
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
1
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Cyclophosphamide is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
Cơ Chế Tác Dụng : Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [PubChem] Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.
Dược Động Học :
▧ Absorption :
After oral administration, peak concentrations occur at one hour.
▧ Volume of Distribution :
30-50 L
▧ Protein binding :
20% of cyclophosphamide is protein bound with no dose dependent changes. Some metabolites are protein bound to an extent greater than 60%.
▧ Metabolism :
Metabolism and activation occurs at the liver. 75% of the drug is activated by cytochrome P450 isoforms, CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18, and 2C19. The CYP2B6 isoform is the enzyme with the highest 4-hydroxylase activity. Cyclophosphamide undergoes activation to eventually form active metabolites, phosphoramide mustard and acrolein. Cyclophosphamide appears to induce its own metabolism which results in an overall increase in clearance, increased formation of 4-hydroxyl metabolites, and shortened t1/2 values following repeated administration.
▧ Route of Elimination :
Cyclophosphamide is eliminated primarily in the form of metabolites. 10-20% is excreted unchanged in the urine and 4% is excreted in the bile following IV administration.
▧ Half Life :
3-12 hours
▧ Clearance :
Total body clearance = 63 ± 7.6 L/kg.
Độc Tính : Adverse reactions reported most often include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea.
Chỉ Định : Cyclophosphamide is indicated for the treatment of malignant lymphomas, multiple myeloma, leukemias, mycosis fungoides (advanced disease), neuroblastoma (disseminated disease), adenocarcinoma of the ovary, retinoblastoma, and carcinoma of the breast. It is also indicated for the treatment of biopsy-proven minimal change nephrotic syndrome in pediatric patients.
Tương Tác Thuốc :
  • Acenocoumarol The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of acenocoumarol.
  • Anisindione The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of anisindione.
  • Belimumab Avoid combination due to enhanced toxic effects of cyclophosphamide.
  • Bendamustine Increases toxicity through pharmacodynamic synergism. Additive myelosuppression.
  • Dicoumarol The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of dicumarol.
  • Digoxin The antineoplasic agent decreases the effect of digoxin
  • Etanercept Avoid combination due to enhanced adverse effects of cyclophosphasmide and increased risk of solid cancer development.
  • Filgrastim Monitor therapy due to adverse effects of cyclophosphamide, especially pulmonary toxicity.
  • Fluconazole Fluconazole reduces metabolism and clearance of cyclophosphamide.
  • Pentostatin Increased toxicity of cyclophosphamide
  • Succinylcholine Cyclophosphamide may increase the effect of succinylcholine.
  • Thiotepa Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Cyclophosphamide, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Cyclophosphamide if Thiotepa is initiated, discontinued or dose changed.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Warfarin The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of warfarin.
Liều Lượng & Cách Dùng : Injection, powder, for solution - Intravenous - 200 mg, 500 mg, 1 g, 2 g
Tablet - Oral - 25 mg, 50 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Sản phẩm biệt dược : Cytoxan
  • Công ty : Actavis
    Sản phẩm biệt dược : Endoxan
  • Công ty :
    Sản phẩm biệt dược : Neosar
  • Công ty : Baxter
    Sản phẩm biệt dược : Procytox
  • Công ty :
    Sản phẩm biệt dược : Revimmune
  • Công ty : Baxter
    Sản phẩm biệt dược : Sendoxan
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00531
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2907
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505441
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07888
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D07760
ChemSpider
http://www.chemspider.com/Chemical-Structure.2804.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0054-4129-25
PharmGKB
http://www.pharmgkb.org/drug/PA449165
Wikipedia
http://en.wikipedia.org/wiki/Cyclophosphamide
RxList
http://www.rxlist.com/cgi/generic3/cyclophosphamide.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cyt1112.shtml
Drugs.com
http://www.drugs.com/cdi/cyclophosphamide.html
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