药品详细
Pentostatin(喷司他丁)
化学结构式图
中文名
喷司他丁
英文名
Pentostatin
分子式
C11H16N4O4
化学名
(8R)-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3H,6H,7H,8H-imidazo[4,5-d][1,3]diazepin-8-ol
分子量
Average: 268.2691
Monoisotopic: 268.11715502
Monoisotopic: 268.11715502
CAS号
53910-25-1
ATC分类
L01X 其它抗肿瘤药
药物类型
small molecule
阶段
approved
商品名
Co-V;Co-Vidarabine;Covidarabine;Nipent;PD-ADI;Vidarbine;Vira a Deaminase Inhibitor;
同义名
2'-DCF;2'-Deoxycoformycin;2'-Dexoycoformycin;Deoxycoformycin;pentostatin;
基本介绍
A potent inhibitor of adenosine deaminase. The drug is effective in the treatment of many lymphoproliferative malignancies, particularly hairy-cell leukemia. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity. [PubChem]
生产厂家
- Bedford laboratories
- Hospira inc
封装厂家
参考
| Synthesis Reference | Not Available |
| General Reference |
剂型
规格
化合物类型
| Type | small molecule |
| Classes |
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| Substructures |
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适应症
Cancer 癌症;
药理
| Indication | For the treatment of hairy cell leukaemia refractory to alpha interferon. |
| Pharmacodynamics | Pentostatin is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia and hairy cell leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase). |
| Mechanism of action | Pentostatin is a potent transition state inhibitor of adenosine deaminase (ADA), the greatest activity of which is found in cells of the lymphoid system. T-cells have higher ADA activity than B-cells, and T-cell malignancies have higher activity than B-cell malignancies. The cytotoxicity that results from prevention of catabolism of adenosine or deoxyadenosine is thought to be due to elevated intracellular levels of dATP, which can block DNA synthesis through inhibition of ribonucleotide reductase. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase). |
| Absorption | Not absorbed orally, crosses blood brain barrier. |
| Volume of distribution | Not Available |
| Protein binding | 4% |
| Metabolism |
Primarily hepatic, but only small amounts are metabolized.
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| Route of elimination | In man, following a single dose of 4 mg/m2 of pentostatin infused over 5 minutes, approximately 90% of the dose was excreted in the urine as unchanged pentostatin and/or metabolites as measured by adenosine deaminase inhibitory activity. |
| Half life | 5.7 hours (with a range between 2.6 and 16 hrs) |
| Clearance |
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| Toxicity | LD50=128 mg/kg (mouse), side effects include lethargy, rash, fatigue, nausea and myelosuppression. |
| Affected organisms |
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| Pathways | Not Available |
理化性质
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| State | solid | ||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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药物相互作用
| Drug | Interaction |
|---|---|
| Cyclophosphamide | Increased toxicity of cyclophosphamide |
| Fludarabine | Unacceptable pulmonary toxicity |
| 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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