Tìm theo
Cisplatin
Các tên gọi khác (4 ) :
  • CDDP
  • Cis-DDP
  • cis-diamminedichloroplatinum(II)
  • Platinol-AQ
Thuốc chống ung thư và tác động vào hệ thống miễn dịch
Thuốc Gốc
Small Molecule
CAS: 15663-27-1
ATC: L01XA01
ĐG : APP Pharmaceuticals , http://www.apppharma.com
CTHH: Cl2H4N2Pt
PTK: 298.035
Cisplatin, cisplatinum or cis-diamminedichloroplatinum(II) (CDDP) is a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas and germ cell tumors. It was the first member of its class, which now also includes carboplatin and oxaliplatin.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
Cl2H4N2Pt
Phân tử khối
298.035
Monoisotopic mass
296.939928001
InChI
InChI=1S/2ClH.2H2N.Pt/h2*1H;2*1H2;/q;;2*-1;+4/p-2
InChI Key
InChIKey=DQLATGHUWYMOKM-UHFFFAOYSA-L
IUPAC Name
dichloroplatinumdiamine
Traditional IUPAC Name
cisplatin
SMILES
N[Pt](N)(Cl)Cl
Độ tan chảy
270 dec °C
Độ hòa tan
2530 mg/L (at 25 °C)
logP
-2.19
pKa (Strongest Basic)
5.06
PSA
52.04 Å2
Refractivity
22.84 m3·mol-1
Polarizability
10.31 Å3
Rotatable Bond Count
0
H Bond Acceptor Count
2
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
0
Bioavailability
1
Rule of Five
true
Dược Lực Học : Cisplatin 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 : Cisplatin, cisplatinum or cis-diamminedichloroplatinum(II) (CDDP) is a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas and germ cell tumors. It was the first member of its class, which now also includes carboplatin and oxaliplatin. 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 :
Following cisplatin doses of 20 to 120 mg/m^2, the concentrations of platinum are highest in liver, prostate, and kidney; somewhat lower in bladder, muscle, testicle, pancreas, and spleen; and lowest in bowel, adrenal, heart, lung, cerebrum, and cerebellum. Platinum is present in tissues for as long as 180 days after the last administration.
▧ Volume of Distribution :
Volume of distribution at steady state = 11-12 L/m^2
▧ Protein binding :
Cisplatin does not undergo instantaneous and reversible binding to plasma protein that is characteristic of normal drug-protein binding. However, the platinum itself is capable of binding to plasma proteins, including albumin, transferrin, and gamma globulin. Three hours after a bolus injection and two hours after the end of a three-hour infusion, 90% of the plasma platinum is protein bound.
▧ Route of Elimination :
The parent compound, cisplatin, is excreted in the urine. Although small amounts of platinum are present in the bile and large intestine after administration of cisplatin, the fecal excretion of platinum appears to be insignificant.
▧ Half Life :
Cisplatin decays monoexponentially with a half life of 20 to 30 minutes following administrations of 50 or 100 mg/m^2. Cisplatin has a plasma half-life of 30 minutes. The complexes between albumin and the platinum from cisplatin do not dissociate to a significant extent and are slowly eliminated with a minimum half-life of five days or more.
▧ Clearance :
* 15-16 L/h/m^2 [total body clearance, 7-hour infusion of 100 mg/m^2] * 62 mL/min/m^2 [renal clearance, 2-hour infusion of 100 mg/m^2] * 50 mL/min/m^2 [renal clearance, 6- to 7-hour infusion of 100 mg/m^2] The renal clearance of free (ultrafilterable) platinum also exceeds the glomerular filtration rate indicating that cisplatin or other platinum-containing molecules are actively secreted by the kidneys. The renal clearance of free platinum is nonlinear and variable and is dependent on dose, urine flow rate, and individual variability in the extent of active secretion and possible tubular reabsorption.
Chỉ Định : For the treatment of metastatic testicular tumors, metastatic ovarian tumors and advanced bladder cancer.
Tương Tác Thuốc :
  • Amikacin Increased risk of nephrotoxicity
  • Bendamustine Increases toxicity through pharmacodynamic synergism. Additive myelosuppression.
  • Bumetanide Increased ototoxicity
  • Cabazitaxel Platinum derivatives such as cisplatin may enhance the myelosuppressive effect of taxane derivatives such as cabazitaxel. Administer taxane derivative before platinum derivative when given as sequential infusions to limit toxicity.Administer paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity. Problems associated with other taxane/platinum combinations are possible, although unsubstantiated. Administering the taxane derivative before the platinum derivative seems prudent.
  • Docetaxel Platinum derivatives such as cisplatin may enhance the myelosuppressive effect of taxane derivatives such as docetaxel. Administer taxane derivative before platinum derivative when given as sequential infusions to limit toxicity. Administer paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity. Problems associated with other taxane/platinum combinations are possible, although unsubstantiated. Administering the taxane derivative before the platinum derivative seems prudent.
  • Ethacrynic acid Increased ototoxicity
  • Fosphenytoin The antineoplasic agent decreases the effect of hydantoin
  • Furosemide Increased ototoxicity
  • Gentamicin Increased risk of nephrotoxicity
  • Leflunomide Immunosuppressants such as cisplatin may enhance the adverse/toxic effect of leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Consider eliminating the use of a leflunomide loading dose in patients who are receiving other immunosuppressants in order to reduce the risk for serious adverse events such as hematologic toxicity. Also, patients receiving both leflunomide and another immunosuppressive medication should be monitored for bone marrow suppression at least monthly throughout the duration of concurrent therapy.
  • Methotrexate Cisplatin increases methotrexate toxicity
  • Natalizumab Immunosuppressants such as cisplatin may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
  • Netilmicin Increased risk of nephrotoxicity
  • Paclitaxel Cisplatin increases the effect and toxicity of paclitaxel
  • Phenytoin The antineoplasic agent decreases the effect of hydantoin
  • Pimecrolimus Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as cisplatin. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
  • Roflumilast Roflumilast may enhance the immunosuppressive effect of immunosuppressants such as cisplatin. The Canadian roflumilast product monograph recommends avoiding concurrent use of roflumilast with any immunosuppressant medications due to the antiinflammatory/immune altering effects of roflumilast and the lack of relevant clinical experience with such use. Of note, this recommendation to avoid concurrent use does not apply to either inhaled corticosteroids (which have much more limited systemic immune-suppressing actions) or short-term systemic corticosteroid use. U.S. prescribing information does not contain this warning; but it appears prudent to avoid this combination when possible.
  • Tacrolimus Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Cisplatin. Use caution during concomitant therapy.
  • Tobramycin Increased risk of nephrotoxicity
  • Topotecan Administration of Topotecan after Cisplatin therapy may increase the risk of hematologic toxicity, such as neutropenia and/or thrombocytopenia. A dose adjustment may be required or the sequence of administration reversed.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Liều Lượng & Cách Dùng : Solution - Intravenous
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Abiplatin
  • Công ty :
    Sản phẩm biệt dược : Cisplatyl
  • Công ty :
    Sản phẩm biệt dược : Platidiam
  • Sản phẩm biệt dược : Platin
  • Công ty :
    Sản phẩm biệt dược : Platinol
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00515
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=441203
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504561
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C06911
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00275
ChemSpider
http://www.chemspider.com/Chemical-Structure.389985.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0015-3072-20
PharmGKB
http://www.pharmgkb.org/drug/PA449014
Wikipedia
http://en.wikipedia.org/wiki/Cisplatin
RxList
http://www.rxlist.com/cgi/generic3/cisplatin.htm
Drugs.com
http://www.drugs.com/cdi/cisplatin.html
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