戊柔比星 | 56124-62-0

• 物质功能分类: 原料药 - 抗肿瘤药 - 抗生素类抗肿瘤药
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 中文名称: 戊柔比星
• 英文名称: valrubicin
• 英文别名: N-(trifluoroacetyl)adriamycin 14-valerate；N-trifluoroacetyldoxorubicin-14-valerate；Valstar；(2S-cis)-2-[1,2,3,4,6,11-hexahydro-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-[[4 2,3,6-trideoxy-3-(trifluoroacetyl)-amino-α-L-lyxo-hexopyranosyl]oxyl]-2-naphthacenyl]-2-oxoethyl pentanoate；N-trifluoroacetyladriamycin-14-valerate；[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-4-[(2R,4S,5S,6S)-5-hydroxy-6-methyl-4-[(2,2,2-trifluoroacetyl)amino]oxan-2-yl]oxy-7-methoxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] pentanoate
• CAS: 56124-62-0
• 化学式: C₃₄H₃₆F₃NO₁₃
• 分子量: 723.654
• InChiKey: ZOCKGBMQLCSHFP-KQRAQHLDSA-N

物化性质

• 熔点：
  116-117 °C
• 沸点：
  135-136 C
• 密度：
  1.3473 (estimate)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• 颜色/状态：
  Orange or orange-red powder

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  51
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  215
• 氢给体数：
  5
• 氢受体数：
  16

ADMET

代谢

曲贝替丁被代谢为两个主要代谢物：N-三氟乙酰阿霉素和N-三氟乙酰阿霉素醇。

Valrubicin is metabolized to two primary metabolites: N-trifluoroacetyladriamycin and N-trifluoroacetyladriamycinol.

来源:DrugBank

代谢

在膀胱内灌注valrubicin后，在2小时的保留期间，药物转化为其主要代谢物，N-三氟乙酰阿霉素和N-三氟乙酰阿霉素醇的量是最小的。2小时保留期后排出灌注液，药物几乎完全排出。大约98.6%的膀胱内给药剂量以原形药物形式从尿液中排出；N-三氟乙酰阿霉素和总蒽环类药物分别占给药剂量的0.4%和99.0%。

Following intravesical instillation of valrubicin, conversion of the drug to its major metabolites, N-trifluoroacetyladriamycin and N-trifluoroacetyladriamycinol, is minimal during the 2 hr retention period. Voiding of the instillate after the 2-hour retention period results in almost complete excretion of the drug. About 98.6% of an intravesical dose of the drug is excreted in the urine unchanged; N-trifluoroacetyladriamycin and total anthracyclines account for 0.4 and 99.0%, respectively, of an administered dose.

来源:Hazardous Substances Data Bank (HSDB)

代谢

主要代谢物是N-三氟乙酰阿霉素和N-三氟乙酰阿霉素醇，它们已在血液中进行了测量。

Major metabolites are N-trifluoroacetyladriamycin and N-trifluoroacetyladriamycinol, which have been measured in blood.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在体内研究中，钙通道阻断剂维拉帕米增强了瓦鲁比星对人类膀胱肿瘤细胞耐药株的活性。

In an in vivo study, the activity of valrubicin against a resistant line of human bladder tumor cells was enhanced by the calcium-channel blocking agent verapamil.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

紧急和支持性措施：保持呼吸道通畅，必要时辅助呼吸。如果出现昏迷、癫痫、低血压和心律不齐，应予以治疗。使用甲氧氯普胺治疗恶心和呕吐，使用静脉晶体液治疗由胃肠炎引起的液体流失。对于骨髓抑制，应在有经验的血液学家或肿瘤学家的帮助下进行治疗。/抗肿瘤药物/

Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, and arrhythmias if they occur. Treat nausea and vomiting with metoclopramide and fluid loss caused by gastroenteritis with intravenous crystalloid fluids. Bone marrow depression should be treated with the assistance of an experienced hematologist or oncologist. /Antineoplastic agents/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

对瓦鲁比辛过量没有已知的解药。

There is no known antidotes to valrubicin over dose.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

Decontamination: Prehospital: 如果有条件，给予活性炭。如果预计在给予活性炭前会有超过60分钟的延迟，考虑使用吐根糖浆诱导呕吐，如果在接触后几分钟内可以给药且没有禁忌症的情况下。Hospital: 给予活性炭。在小剂量摄入后，如果可以迅速给予活性炭，则不需要胃排空。/抗肿瘤药物/

Decontamination: Prehospital: Administer activated charcoal, if available. If a delay of more than 60 minutes is expected before charcoal can be given, consider using ipecac to induce vomiting. If it can be administered within a few minutes of exposure and there are no contraindications. Hospital: Administer activated charcoal. Gastric emptying is not necessary after a small ingestion if activated charcoal can be given promptly. /Antineoplastic agents/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 医疗监测

/抗癌药物的预防措施：/目前没有可用于常规监测人员接触危险药物证据的方法。检测诱变剂或染色体损伤的测试并非针对特定药物，且仅在控制性研究中具有价值。对尿液中存在危险药物的化学分析，在需要检测职业暴露的灵敏度水平上，仅限于少数药物，且尚未在商业上可用。/抗癌药物/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ There is no method available for routine monitoring of personnel for evidence of hazardous drug exposure. Tests for the presence of mutagens or chromosomal damage are not drug specific and are of value only in controlled studies. Chemical analysis of urine for the presence of hazardous drugs at the sensitivity level needed to detect occupational exposure is limited to a few drugs and is not yet commercially available. /Antineoplastic agents/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

经膀胱内给药800毫克valrubicin并在膀胱内保留2小时后，对于膀胱原位癌（CIS）患者……药物仅有极少量被吸收进入血浆；valrubicin的代谢物也已在血浆中检测到。在膀胱内每周一次给予200至900毫克valrubicin的膀胱原位癌或Ta、T1或T2期膀胱癌患者中，第一次、第三次和第六次给药后6小时内，检测到valrubicin及其代谢物的低血浆浓度……。

Following intravesical administration of 800 mg valrubicin and retention in the bladder for a period of 2-hours in patients with carcinoma in situ (CIS) of the bladder ... minimal amounts of the drug are absorbed into the plasma; metabolites of valrubicin also have been detected in plasma. Following intravesical administration of 200 to 900 mg valrubicin once weekly in patients with CIS of the bladder or stage Ta, T1, or T2 bladder cancer low plasma concentrations of valrubicin and its metabolites, ... were detected within 6 hours after administration of the first, third and sixth doses of the drug.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

消除：几乎完全通过排空灌入物。

Elimination: Almost entirely by voiding the instillate.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

长春瑞滨（Valrubicin）通过膀胱内给药后能轻易渗透进入膀胱细胞壁。任何系统性吸收的程度取决于膀胱壁的状况。血清浓度通常非常低（纳克量级），即使在广泛的经尿道切除术后，尽管曾有一个案例报告，在给一个膀胱穿孔的患者给药后，其浓度与静脉给药后达到的浓度相似。

Valrubicin penetrates easily into the bladder cell wall after intravesical administration. The degree of any systemic absorption depends on the condition of the bladder wall. Serum concentration usually are very low (nanogram quantities), even after extensive transurethral resection, although a case has been reported in which concentrations after administration to a patient with a perforated bladder were similar to those achieved after intravenous administration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尚不清楚长春瑞滨是否分布在人乳中。

It is not known whether valrubicin is distributed in breast milk.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

... Valrubicin比多柔比星更迅速地进入体外细胞。当将Valrubicin通过膀胱内给药给膀胱癌患者时，药物的细胞毒浓度渗透到了膀胱的浅层肌肉。...

... Valrubicin entered individual cells more rapidly than doxorubicin in vitro. When valrubicin was administered intravesically to patients with bladder cancer, cytotoxic concentrations of the drug penetrated the superficial muscle layer of the bladder. ...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2941906000
• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P201,P202,P264,P270,P280,P301+P312+P330,P308+P313,P405,P501
• 危险品运输编号：
  2811
• 危险性描述：
  H302,H340,H350,H360
• 储存条件：
  2-8℃