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药品详细

Thiotepa(塞替派)

化学结构式图
中文名
塞替派
英文名
Thiotepa
分子式
C6H12N3PS
化学名
tris(aziridin-1-yl)-$l^{5}-phosphanethione
分子量
Average: 189.218
Monoisotopic: 189.048954601
CAS号
52-24-4
ATC分类
L01A 烷化剂
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

N,N’N’-triethylenethiophosphoramide (ThioTEPA) is a cancer chemotherapeutic member of the alkylating agent group, now in use for over 50 years. It is a stable derivative of N,N’,N’’- triethylenephosphoramide (TEPA). It is mostly used to treat breast cancer, ovarian cancer and bladder cancer. It is also used as conditioning for Bone marrow transplantation. Its main toxicity is myelosuppression.

生产厂家
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Immunex corp
  • Teva parenteral medicines inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Maanen MJ, Smeets CJ, Beijnen JH: Chemistry, pharmacology and pharmacokinetics of N,N’,N" -triethylenethiophosphoramide (ThioTEPA). Cancer Treat Rev. 2000 Aug;26(4):257-68. Pubmed
  2. Maanen MJ, Smeets CJ, Beijnen JH: Chemistry, pharmacology and pharmacokinetics of N,N’,N" -triethylenethiophosphoramide (ThioTEPA). Cancer Treat Rev. 2000 Aug;26(4):257-68. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes Not Available
Substructures Not Available
适应症
药理
Indication ThioTEPA is used a as conditioning treatment prior to allogeneic or autologous haematopoietic progenitor cell transplantation (HPCT) in haematological diseases in adult and paediatric patients. Also, when high dose chemotherapy with HPCT support it is appropriate for the treatment of solid tumours in adult and paediatric patients.
Pharmacodynamics The unstable nitrogen-carbon groups alkylate with DNA causing irrepairable DNA damage. They stop tumor growth by crosslinking guanine nucleobases 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. These drugs act nonspecifically.
Mechanism of action The alkyl group is attached to the guanine base of DNA, at the number 7 nitrogen atom of the imidazole ring. They stop tumor growth by crosslinking guanine nucleobases 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. These drugs act nonspecifically.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Not Available
Route of elimination Urinary excretion of 14C-labeled thiotepa and metabolites in a 34-year old patient with metastatic carcinoma of the cecum who received a dose of 0.3 mg/kg intravenously was 63%.
Half life 1.5 to 4.1 hours
Clearance
  • 446 +/- 63 mL/min [female patients (45 to 84 years) with advanced stage ovarian cancer receiving 60 mg and 80 mg thiotepa by intravenous infusion on subsequent courses given at 4-week intervals]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 51.5 °C PhysProp
water solubility 1.9E+005 mg/L (at 25 °C) MERCK INDEX (1996)
logP 0.53 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 9.27e+00 g/l ALOGPS
logP 0.17 ALOGPS
logP -1 ChemAxon
logS -1.3 ALOGPS
pKa (strongest basic) -0.3 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 9.03 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 50.72 ChemAxon
polarizability 18.3 ChemAxon
药物相互作用
Drug Interaction
Bendamustine Increases toxicity through pharmacodynamic synergism. Additive myelosuppression.
Bupropion Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Bupropion, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Bupropion if Thiotepa is initiated, discontinued or dose changed.
Cyclophosphamide 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.
Fosphenytoin Possible increase in thiotepa levels
Irinotecan Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Irinotecan, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Irinotecan if Thiotepa is initiated, discontinued or dose changed.
Ketamine Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Ketamine, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Ketamine if Thiotepa is initiated, discontinued or dose changed.
Natalizumab The immunosuppressant, Thiotepa, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
Phenytoin Possible increase in thiotepa levels
Promethazine Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Promethazine, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Promethazine if Thiotepa is initiated, discontinued or dose changed.
Selegiline Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Selegiline, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Selegiline 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.
食物相互作用
Not Available

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