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药品详细

Oxaliplatin(奥沙利铂)

化学结构式图
中文名
奥沙利铂
英文名
Oxaliplatin
分子式
C8H12N2O4Pt
化学名
(3aR,7aR)-octahydro-2',5'-dioxaspiro[cyclohexa[d]1,3-diaza-2-platinacyclopentane-2,1'-cyclopentane]-3',4'-dione
分子量
Average: 395.276
Monoisotopic: 395.044481331
CAS号
61825-94-3
ATC分类
L01X 其它抗肿瘤药
药物类型
small molecule
阶段
approved
商品名
Eloxatin (Sanofi-Aventis);
同义名
oxaliplatin;Oxaliplatin [Usan:Inn:Ban];Oxaliplatino [Spanish];Oxaliplatinum [Latin];Oxaloplatine [French];Oxaloplatino [Spanish];
基本介绍

Oxaliplatin is a platinum-based chemotherapy drug in the same family as cisplatin and carboplatin. It is typically administered in combination with fluorouracil and leucovorin in a combination known as Folfox for the treatment of colorectal cancer. Compared to cisplatin the two amine groups are replaced by cyclohexyldiamine for improved antitumour activity. The chlorine ligands are replaced by the oxalato bidentate derived from oxalic acid in order to improve water solubility. Oxaliplatin is marketed by Sanofi-Aventis under the trademark Eloxatin®.

生产厂家
  • App pharmaceuticals llc
  • Ebewe pharma ges mbh nfg kg
  • Fresenius kabi oncology plc
  • Hospira inc
  • Hospira worldwide pty
  • Sanofi aventis us llc
  • Sun pharma global inc
  • Teva parenteral medicines inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Pasetto LM, D’Andrea MR, Rossi E, Monfardini S: Oxaliplatin-related neurotoxicity: how and why? Crit Rev Oncol Hematol. 2006 Aug;59(2):159-68. Epub 2006 Jun 27. Pubmed
  2. Graham J, Mushin M, Kirkpatrick P: Oxaliplatin. Nat Rev Drug Discov. 2004 Jan;3(1):11-2. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Keto-Acids
Substructures
  • Anions
  • Acetates
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
  • Keto-Acids
  • Cations
适应症
Cancer 癌症;
药理
Indication Used in combination with infusional 5-FU/LV, is indicated for the treatment of advanced carcinoma of the colon or rectum and for adjuvant treatment of stage III colon cancer patients who have undergone complete resection of the primary tumor.
Pharmacodynamics Oxaliplatin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of Oxaliplatin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed.
Mechanism of action After activation, oxaliplatin binds preferentially to the guanine and cytosine moieties of DNA, leading to cross-linking of DNA, thus inhibiting DNA synthesis and function.
Absorption Bioavailability is complete following intravenous administration.
Volume of distribution
  • 440 L
Protein binding Plasma protein binding of platinum (active metabolite) is irreversible and is greater than 90%.
Metabolism
Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. There is no evidence of cytochrome P450-mediated metabolism in vitro.
Route of elimination The major route of platinum elimination is renal excretion. At five days after a single 2-hour infusion of oxaliplatin, urinary elimination accounted for about 54% of the platinum eliminated, with fecal excretion accounting for only about 2%.
Half life Approximately 10 - 25 minutes
Clearance Not Available
Toxicity There have been five cases of oxaliplatin overdose reported. One patient received two 130 mg/m2 doses of oxaliplatin (cumulative dose of 260 mg/m2) within a 24-hour period. The patient experienced Grade 4 thrombocytopenia (<25,000/mm3) without any bleeding, which resolved. Two other patients were mistakenly administered oxaliplatin instead of carboplatin. One patient received a total oxaliplatin dose of 500 mg and the other received 650 mg. The first patient experienced dyspnea, wheezing, paresthesia, profuse vomiting and chest pain on the day of administration. She developed respiratory failure and severe bradycardia, and subsequently did not respond to resuscitation efforts. The other patient also experienced dyspnea, wheezing, paresthesia, and vomiting.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 1.24e+01 g/l ALOGPS
logP 0.04 ALOGPS
logP 1.73 ChemAxon
logS -1.5 ALOGPS
pKa (strongest basic) 5.88 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 76.66 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 65.92 ChemAxon
polarizability 21.29 ChemAxon
药物相互作用
Drug Interaction
Bendamustine Increases toxicity through pharmacodynamic synergism. Additive myelosuppression.
Topotecan Administration of Topotecan after Oxaliplatin 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.
食物相互作用
Not Available

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