用户名： 密   码：
注册 | 忘记密码？
药品详细

Irinotecan (伊立替康 )

化学结构式图
中文名
伊立替康
英文名
Irinotecan
分子式
Not Available
化学名
(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.0^{2,11}.0^{4,9}.0^{15,20}]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl 4-(piperidin-1-yl)piperidine-1-carboxylate
分子量
Average: 586.678
Monoisotopic: 586.279134968
CAS号
100286-90-6
ATC分类
L01X 其它抗肿瘤药
药物类型
small molecule
阶段
商品名
Camptosar;CP0;IRINOTECAN, CPT-11;
同义名
irinotecan;Irinotecan Hcl;Irinotecan Hydrochloride;Irinotecan Hydrochloride Trihydrate;Irinotecanum [INN-Latin];
基本介绍

Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. It is a derivative of camptothecin that inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex, and causes double-strand DNA breakage and cell death.

生产厂家
  • Accord healthcare inc
  • Actavis totowa llc
  • Akorn inc
  • App pharmaceuticals
  • Bedford laboratories
  • Dr reddys laboratories ltd
  • Ebewe pharma ges mbh nfg kg
  • Fresenius kabi oncology plc
  • Hospira inc
  • Pfizer inc
  • Pharmaforce inc
  • Pliva lachema as
  • Sandoz inc
  • Sun pharma global inc
  • Teva parenteral medicines inc
  • Watson laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ: Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol. 2004 Apr 15;22(8):1382-8. Epub 2004 Mar 8. Pubmed
  2. O’Dwyer PJ, Catalano RB: Uridine diphosphate glucuronosyltransferase (UGT) 1A1 and irinotecan: practical pharmacogenomics arrives in cancer therapy. J Clin Oncol. 2006 Oct 1;24(28):4534-8. Pubmed
  3. Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  4. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed
剂型
Form Route Strength
Solution Intravenous
规格
Unit description Cost Unit
Irinotecan hcl 40 mg/2 ml inj 138.07 USD ml
Camptosar 20 mg/ml vial 36.0 USD ml
Irinotecan hcl 40 mg/2 ml vial 22.2 USD ml
化合物类型
Type small molecule
Classes
  • Camptothecins
Substructures
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Pyrans
  • Acetates
  • Carbamates and Derivatives
  • Phenols and Derivatives
  • Lactones
  • Pyridines and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Bipyridines
  • Hydroxyquinolines
  • Camptothecins
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Pyridines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • (Iso)quinolines and Derivatives
  • Imines
  • Phenyl Esters
  • Piperidines
适应症
Cancer 癌症;
药理
Indication For the treatment of metastatic colorectal cancer (first-line therapy when administered with 5-fluorouracil and leucovorin). Also used in combination with cisplatin for the treatment of extensive small cell lung cancer. Irinotecan is currently under investigation for the treatment of metastatic or recurrent cervical cancer.
Pharmacodynamics Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is a semisynthetic derivative of camptothecin. Camptothecins interact specifically with topoisomerase I, an enzyme in the cell nucleus that regulates DNA topology and facilitates nuclear processes such as DNA replication, recombination, and repair. During these processes, topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks, allowing single DNA strands to pass through the break. The 3'-DNA terminus of the broken DNA strands bind covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After the DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the chemically unaltered topoisomers that allow transcription to proceed. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks. The precise contribution of SN-38 to the activity of irinotecan in humans is not known. Irinotecan is cell cycle phase-specific (S-phase).
Mechanism of action Irinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex. The formation of this ternary complex interferes with the moving replication fork, which induces replication arrest and lethal double-stranded breaks in DNA. As a result, DNA damage is not efficiently repaired and apoptosis (programmed cell death) occurs.
Absorption 100%
Volume of distribution Not Available
Protein binding 30%-68%
Metabolism

Hepatic
Route of elimination The cumulative biliary and urinary excretion of irinotecan and its metabolites (SN-38 and SN-38 glucuronide) over a period of 48 hours following administration of irinotecan in two patients ranged from approximately 25% (100 mg/m2) to 50% (300 mg/m2).
Half life 6-12 hours
Clearance Not Available
Toxicity Gastrointestinal complications, such as nausea, vomiting, abdominal cramping, diarrhea, and infection.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00433 Irinotecan Pathway SMP00433
理化性质
Properties
State solid
Melting point 222-223 oC
Experimental Properties
Property Value Source
water solubility Soluble PhysProp
logP 3.2 PhysProp
Predicted Properties
Property Value Source
water solubility 1.07e-01 g/l ALOGPS
logP 3.94 ALOGPS
logP 2.78 ChemAxon Molconvert
logS -3.74 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 112.51 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 161.33 ChemAxon Molconvert
polarizability 65.27 ChemAxon Molconvert
药物相互作用
Drug Interaction
Aprepitant Aprepitant may change levels of the chemotherapy agent, irinotecan.
Atazanavir Increases levels/effect of irinotecan
Fosphenytoin The hydantoin decreases the effect of irinotecan
Ketoconazole Ketoconazole increases the effect and toxicity of irinotecan
Phenytoin The hydantoin decreases the effect of irinotecan
Telithromycin Telithromycin may reduce clearance of Irinotecan. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Irinotecan if Telithromycin is initiated, discontinued or dose changed.
Thiotepa 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.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of irinotecan by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of irinotecan if voriconazole is initiated, discontinued or dose changed.
食物相互作用
Not Available

返回 | 收藏