Irinotecan hydrochloride
(Synonyms: 伊立替康盐酸盐; (+)-Irinotecan hydrochloride; CPT-11 hydrochloride) 目录号 : GC36329
A potent inhibitor of DNA topoisomerase I
Cas No.:100286-90-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Irinotecan, a derivative of the alkaloid camptothecin , functions as a prodrug that is converted by tissue carboxylesterase to 7-
1.Rothenberg, M.L.Topoisomerase I inhibitors: Review and updateAnn. Oncol.8(9)837-855(1997) 2.Dancey, J., and Eisenhauer, E.A.Current perspectives on camptothecins in cancer treatmentBr. J. Cancer74(3)327-338(1996) 3.Mathijssen, R.H.J., van Alphen, R.J., Verweij, J., et al.Clinical pharmacokinetics and metabolism of irinotecan (CPT-11)Clin. Cancer Res.7(8)2182-2194(2001) 4.Ma, M.K., and McLeod, H.L.Lessons learned from the irinotecan metabolic pathwayCurr. Med. Chem.10(1)41-49(2003)
| Cas No. | 100286-90-6 | SDF | |
| 别名 | 伊立替康盐酸盐; (+)-Irinotecan hydrochloride; CPT-11 hydrochloride | ||
| Canonical SMILES | O=C(N1CCC(N2CCCCC2)CC1)OC3=CC=C4N=C5C(CN6C(C(COC([C@@]7(CC)O)=O)=C7C=C65)=O)=C(CC)C4=C3.[H]Cl | ||
| 分子式 | C33H39ClN4O6 | 分子量 | 623.14 |
| 溶解度 | DMSO: ≥ 51 mg/mL (81.84 mM); Water: 3.33 mg/mL (5.34 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6048 mL | 8.0239 mL | 16.0478 mL |
| 5 mM | 0.321 mL | 1.6048 mL | 3.2096 mL |
| 10 mM | 0.1605 mL | 0.8024 mL | 1.6048 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pegylated Liposomal Irinotecan hydrochloride Trihydrate for Treating Pancreatic Cancer After Gemcitabine: An Evidence Review Group Perspective of a NICE Single Technology Appraisal
Pharmacoeconomics 2018 Mar;36(3):289-299.PMID:29178025DOI:10.1007/s40273-017-0592-3.
The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Shire Pharmaceuticals) of pegylated liposomal Irinotecan hydrochloride trihydrate (liposomal irinotecan) to submit clinical and cost-effectiveness evidence for its use in combination with 5-fluorouracil (5-FU) and folic acid/leucovorin (LV) for treating patients with pancreatic cancer following prior treatment with gemcitabine as part of the institute's Single Technology Appraisal process. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article presents a summary of the company's evidence, the ERG review and the resulting NICE guidance (TA440), issued on 26 April 2017. Clinical evidence for liposomal irinotecan + 5-FU/LV versus 5-FU/LV was derived from 236 patients with metastatic pancreatic cancer in the multinational, open-label, randomised controlled NAPOLI-1 trial. Results from analyses of progression-free survival and overall survival showed statistically significant improvements for patients treated with liposomal irinotecan + 5-FU/LV compared with those treated with 5-FU/LV. However, 5-FU/LV alone is rarely used in National Health Service clinical practice for patients with metastatic pancreatic cancer previously treated with gemcitabine. The company, ERG and Appraisal Committee (AC) all agreed that oxaliplatin + 5-FU/LV is the most commonly used treatment. Oxaliplatin + 5-FU/LV was compared with 5-FU/LV in two trials identified by the company. However, the company and the ERG both considered attempts to compare the efficacy of liposomal irinotecan + 5-FU/LV with oxaliplatin + 5-FU/LV to be methodologically flawed; not only was there heterogeneity between trials and their populations but also the proportional hazards assumption required to conduct a robust indirect treatment comparison (ITC) was violated. Nonetheless, data derived from an ITC were used to inform the company's economic model. Using the discounted patient access scheme price for liposomal irinotecan + 5-FU/LV, the company reported an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of £54,412 for the comparison with oxaliplatin + 5-FU/LV. The ERG considered that the company's base-case cost-effectiveness results for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV were underestimates and should be interpreted with extreme caution. Following implementation of a number of model amendments, the ERG's modified exploratory ICER for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV was £106,898 per QALY gained. The AC accepted the majority of the ERG's amendments to the model, and also highlighted that the total QALYs for oxaliplatin + 5-FU/LV were lower than for 5-FU/LV in the company's model, which the AC considered to be clinically implausible. The AC therefore considered results from exploratory analyses, undertaken by the ERG, which included altering the QALY difference between liposomal irinotecan + 5-FU/LV and oxaliplatin + 5-FU/LV by ± 10%. These analyses resulted in ICERs for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV of between £201,019 per QALY gained to liposomal irinotecan + 5-FU/LV being dominated by oxaliplatin + 5-FU/LV. Therefore, despite uncertainty around the clinical-effectiveness evidence and cost-effectiveness results, the AC was confident that the ICER was in excess of £50,000 per QALY gained. The final guidance issued by NICE is that liposomal irinotecan + 5-FU/LV is not recommended within its marketing authorisation for treating metastatic adenocarcinoma of the pancreas in adults whose disease has progressed after gemcitabine-based therapy.
[Irinotecan hydrochloride (CPT-11)]
Gan To Kagaku Ryoho 1994 Apr;21(5):709-17.PMID:8154899doi
Irinotecan hydrochloride (CPT-11) is a water-soluble semisynthetic derivative of camptothecin. CPT-11 is a prodrug that undergoes deesterification in vivo to produce SN-38, a metabolite that is 1,000-fold more potent than the parent compound in vitro. CPT-11 is a potent topoisomerase I inhibitor with a broad spectrum of experimental antitumor activity. Recent clinical trials also reveal that CPT-11 is very effective in the treatment of cancers including lung cancer, cervix cancer, ovary cancer, etc. Now, comparative trials of combination chemotherapy in responsive tumors are indicated from these excellent clinical results.
Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer
N Engl J Med 2002 Jan 10;346(2):85-91.PMID:11784874DOI:10.1056/NEJMoa003034.
Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. In a phase 2 study of irinotecan plus cisplatin in patients with extensive small-cell lung cancer, there was a high response rate and a promising median survival time. Methods: We conducted a multicenter, randomized, phase 3 study in which we compared irinotecan plus cisplatin with etoposide plus cisplatin in patients with extensive (metastatic) small-cell lung cancer. Results: The planned size of the study population was 230 patients, but enrollment was terminated early because an interim analysis found a statistically significant difference in survival between the patients assigned to receive irinotecan and cisplatin and those assigned to receive etoposide and cisplatin; as a result, only 154 patients were enrolled. The median survival was 12.8 months in the irinotecan-plus-cisplatin group and 9.4 months in the etoposide-plus-cisplatin group (P=0.002 by the unadjusted log-rank test). At two years, the proportion of patients surviving was 19.5 percent in the irinotecan-plus-cisplatin group and 5.2 percent in the etoposide-plus-cisplatin group. Severe or life-threatening myelosuppression was more frequent in the etoposide-plus-cisplatin group than in the irinotecan-plus-cisplatin group, and severe or life-threatening diarrhea was more frequent in the irinotecan-plus-cisplatin group than in the etoposide-plus-cisplatin group. Conclusions: Irinotecan plus cisplatin is an effective treatment for metastatic small-cell lung cancer.
Irinotecan hydrochloride: drug profile and nursing implications of a topoisomerase I inhibitor in patients with advanced colorectal cancer
Oncol Nurs Forum 1998 Apr;25(3):535-43.PMID:9568608doi
Purpose/objectives: To review the drug profile and nursing implications of the topoisomerase I inhibitor Irinotecan hydrochloride. Data sources: Published articles, abstracts, professional communications, drug manufacturer, and professional clinical experience with irinotecan clinical studies. Data synthesis: Irinotecan, one of the first topoisomerase I inhibitors to gain wide clinical use, has exhibited activity in several malignancies. In June 1996, the United States Food and Drug Administration approved its use in patients with metastatic colorectal cancer refractory to fluorouracil (5-FU)-based therapy. The recommended starting dose is 125 mg/m2 administered as a weekly infusion for four weeks followed by a two-week rest period. The most common and clinically significant adverse events include diarrhea, neutropenia, and nausea and vomiting. Other adverse events include alopecia and fatigue. Conclusions: Irinotecan has significant activity in patients with 5-FU-refractory colorectal cancer. This drug is well tolerated and easily administered in an outpatient setting. The most common adverse events are well characterized and are reversible upon treatment discontinuation or dosage reduction. In particular, diarrhea, the most common toxicity, is manageable with use of appropriate dose modification and rigorous administration of loperamide at the first signs of diarrhea. Implications for nursing practice: Nurses need to focus on identifying and managing adverse effects based on individual patient tolerance. Nurses have an important role to play in patient education and follow up in order to minimize toxicity. Patient care concerns include management of diarrhea and nausea and vomiting, neutropenia with related risk of infection, and fluid and electrolyte imbalances.
Clinical trials of Irinotecan hydrochloride (CPT, campto injection, topotecin injection) in Japan
Ann N Y Acad Sci 1996 Dec 13;803:292-305.PMID:8993523DOI:10.1111/j.1749-6632.1996.tb26399.x.
CPT-11 was synthesized in 1984 at the laboratory of Yakult Honsha. Phase I study of CPT-11 was begun in 1986. The appropriate doses for phase II studies were decided to be 100 mg/m2 weekly or 150 mg/m2 every 2 weeks. Phase II study was conducted and this drug was approved for NSCLC, SCLC, uterine cancer and ovarian cancer by MHW in 1994. It obtained approval for stomach cancer, colorectal cancer, breast cancer, skin cancer and non-Hodgkin's lymphoma in 1995. The combination chemotherapies including CPT-11 have been conducted by using various regimens such as CPT-11 + CDDP, CPT-11 + VP-16, CPT-11 + 5-FU and CBDCA + CPT-11. In stage IV SCLC two prospective randomized controlled trials are on going comparing CPT-11 vs. CPT-11 + CDDP vs. VDS + CDDP and CPT-11 + CDDP vs. VDS + CDDP. In advanced SCLC Japanese Clinical Oncology Group (JCOG) started a randomized controlled trial comparing CPT-11 + CDDP vs. VP-16 + CDDP. In stage III NSCLC the dose escalation studies of CPT-11 (CPT-11) in the combination with TRT are ongoing by JCOG. The problem of CPT-11 in the combination chemotherapy and combined modality is that it is quite difficult to increase the dose of CPT-11 to full dose to obtain the maximum effect.