(7S,9S)-7-[(2R,5R)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: (7S,9S)-7-[(2R,5R)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione
• 化学式: C₂₇H₂₉NO₁₁
• 分子量: 543.5
• InChiKey: AOJJSUZBOXZQNB-DMDRFMAZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  206
• 氢给体数：
  6
• 氢受体数：
  12

ADMET

代谢

表柔比星在肝脏中被广泛且迅速代谢，同时也被包括红细胞在内的其他器官和细胞代谢。已经确定了四种主要的代谢途径：(1) C-13位酮基还原形成13(S)-二氢衍生物，表柔比星酚；(2) 未改变的药物和表柔比星酚与葡萄糖醛酸结合；(3) 通过水解过程失去氨基糖部分，形成多柔比星和多柔比星酚的苷元；(4) 通过氧化还原过程失去氨基糖部分，形成7-脱氧多柔比星苷元和7-脱氧多柔比星酚苷元。表柔比星酚的体外细胞毒性活性是表柔比星的十分之一。由于表柔比星酚的血浆水平低于未改变的药物，它们不太可能达到体内产生细胞毒性的足够浓度。其他代谢物没有报告出显著的活性或毒性。

Epirubicin is extensively and rapidly metabolized by the liver and is also metabolized by other organs and cells, including red blood cells. Four main metabolic routes have been identified: (1) reduction of the C-13 keto-group with the formation of the 13(S)-dihydro derivative, epirubicinol; (2) conjugation of both the unchanged drug and epirubicinol with glucuronic acid; (3) loss of the amino sugar moiety through a hydrolytic process with the formation of the doxorubicin and doxorubicinol aglycones; and (4) loss of the amino sugar moiety through a redox process with the formation of the 7-deoxy-doxorubicin aglycone and 7-deoxy-doxorubicinol aglycone. Epirubicinol has in vitro cytotoxic activity one-tenth that of epirubicin. As plasma levels of epirubicinol are lower than those of the unchanged drug, they are unlikely to reach in vivo concentrations sufficient for cytotoxicity. No significant activity or toxicity has been reported for the other metabolites.

来源:Hazardous Substances Data Bank (HSDB)

代谢

次级醇代谢物被认为是多柔比星（阿霉素，DOX）和其他抗癌蒽环类药物引起慢性心脏毒性的介质。在本研究中，添加了NADPH的人心胞质被发现可以还原多柔比星四环侧链上的羰基，产生次级醇代谢物多柔比星醇（DOXol）。当用表柔比星（EPI）替代多柔比星时，发现醇代谢物形成的水平降低，EPI是一种心脏毒性较低的光学异构体，特点是在与四环相连的氨基糖（道诺糖胺）的C-4位置上，羟基从轴向构型变为赤道构型。当用MEN替代多柔比星时，也观察到了类似的降低，MEN是一种新型蒽环类药物，具有减少心脏毒性的临床前证据。MEN的特点是四环上C-4位置缺少一个甲氧基团，并且在道诺糖胺和苷元之间插入了2,6-去氧-L-岩藻糖。与甲氧基或4-去甲氧基苷元以及许多单糖或二糖4-去甲氧基蒽环类药物的多重比较表明，缺乏甲氧基团和存在二糖单元都限制了MEN醇代谢物的形成。使用酶促生成的或纯化的蒽环类药物次级醇的研究还表明，存在二糖单元，而不是缺乏甲氧基团，使得MEN的代谢物与细胞质乌头酸酶的[4Fe-4S]簇反应性降低，这通过其被还原为母体羰基蒽环类药物的限量以及Fe(II)从簇中分散程度的降低得到证明。总的来说，这些研究（i）描述了甲氧基和糖取代基对蒽环类药物次级醇的形成和[4Fe-4S]反应性的不同影响，（ii）支持醇代谢物在蒽环类药物引起的心脏毒性中的作用，因为它们证明了心脏毒性较低的地塞米松和MEN 10755在形成这类代谢物的水平上有所降低，以及（iii）建议MEN的心脏毒性可能通过其醇代谢物降低的[4Fe-4S]反应性而进一步降低。

Secondary alcohol metabolites have been proposed to mediate chronic cardiotoxicity induced by doxorubicin (DOX) and other anticancer anthracyclines. In this study, NADPH-supplemented human cardiac cytosol was found to reduce the carbonyl group in the side chain of the tetracyclic ring of doxorubicin, producing the secondary alcohol metabolite doxorubicinol (DOXol). A decrease in the level of alcohol metabolite formation was observed by replacing doxorubicin with epirubicin (EPI), a less cardiotoxic analogue characterized by an axial-to-equatorial epimerization of the hydroxyl group at C-4 in the amino sugar bound to the tetracyclic ring (daunosamine). A similar decrease was observed by replacing doxorubicin with MEN, a novel anthracycline with preclinical evidence of reduced cardiotoxicity. MEN is characterized by the lack of a methoxy group at C-4 in the tetracyclic ring and by intercalation of 2, 6-dideoxy-L-fucose between daunosamine and the aglycone. Multiple comparisons with methoxy- or 4-demethoxyaglycones, and a number of mono- or disaccharide 4-demethoxyanthracyclines, showed that both the lack of the methoxy group and the presence of a disaccharide moiety limited alcohol metabolite formation by MEN. Studies with enzymatically generated or purified anthracycline secondary alcohols also showed that the presence of a disaccharide moiety, but not the lack of a methoxy group, made the metabolite of MEN less reactive with the [4Fe-4S] cluster of cytoplasmic aconitase, as evidenced by its limited reoxidation to the parent carbonyl anthracycline and by a reduced level of delocalization of Fe(II) from the cluster. Collectively, these studies (i) characterize the different influence of methoxy and sugar substituents on the formation and [4Fe-4S] reactivity of anthracycline secondary alcohols, (ii) lend support to the role of alcohol metabolites in anthracycline-induced cardiotoxicity, as they demonstrate that the less cardiotoxic EPI and MEN 10755 share a reduction in the level of formation of such metabolites, and (iii) suggest that the cardiotoxicity of MEN might be further decreased by the reduced [4Fe-4S] reactivity of its alcohol metabolite.

来源:Hazardous Substances Data Bank (HSDB)

代谢

许多抗癌药物被发现具有致癌性、致突变性和致畸性潜力。该研究的目的是对定期参与制备细胞毒剂物的医院药房人员进行细胞遗传学和内剂量监测，以测试在常规工作条件下由于职业暴露以及意外污染情况下可能的细胞毒素诱导的遗传毒性效应。...通过测量全血中的铂和血浆中的蒽环类药物来评估对细胞毒素的内部暴露。使用微核试验和姐妹染色单体交换分析在外周血淋巴细胞中确定细胞遗传损伤的水平。在2年的时间里进行了五轮监测。...在职业暴露受试者与对照组之间，姐妹染色单体交换（SCE）和微核（MN）的平均频率没有显著差异（9.9 +/- 1.4 对 10.1 +/- 1.2 SCEs/细胞和21.2 +/- 7.2 对 23.3 +/- 7.5 MN/2000双核细胞，n = 16）。在12起工作场所意外污染中有7起检测到SCE或MN的显著升高，而在这些受试者中没有观察到血液中铂和血浆中蒽环类的增加。通过测量血浆中的表柔比星，确定了两个未报告的污染案例。发现吸烟显著增加了SCE。个人SCE评分和MN评分之间没有观察到相关性。.../作者/的研究结果支持在意外污染情况下相关暴露于细胞毒素药物后SCE或MN的短暂增加。医院药房人员与对照组之间SCE和MN没有显著差异，这表明相应工作场所的安全标准很高。

Many antineoplastic drugs were found to have carcinogenic, mutagenic and teratogenic potential. The aim of this study was to carry out cytogenetic and internal dose monitoring of hospital pharmacy personnel regularly involved in the preparation of cytostatic agents, in order to test possible cytostatics-induced genotoxic effects due to occupational exposure under routine working conditions, and in cases of accidental contamination. ... Platinum in whole blood and anthracyclines in plasma were measured to assess internal exposure to cytostatics. The level of cytogenetic damage was determined in peripheral blood lymphocytes with the micronucleus test and the sister chromatid exchange assay. Five series of monitoring were performed over a period of 2 years. ... No significant differences in the mean frequencies of sister chromatid exchanges (SCE) and micronuclei (MN) were found between occupationally exposed probands and controls (9.9 +/- 1.4 vs 10.1 +/- 1.2 SCEs/cell and 21.2 +/- 7.2 vs 23.3 +/- 7.5 MN/2000 binucleated (BN) cells, n = 16). Significant elevations of SCE or MN were detected in seven out of 12 cases of accidental contamination at the workplace, whereas no increase in platinum in blood and anthracyclines in plasma was observed in these probands. Two cases of non-reported contamination were identified by measurement of epirubicin in plasma. Smoking was found to increase the SCE significantly. No correlation between individual SCE scores and MN scores was observed. ... /The authors/ findings support a transient increase in SCE or MN after relevant exposure to cytostatic drugs in cases of accidental contamination. The lack of significant differences in SCE and MN between hospital pharmacy personnel and unexposed controls, points to high standards of safety at the corresponding workplaces.

来源:Hazardous Substances Data Bank (HSDB)

代谢

有令人信服的体外证据表明，仅基于血浆浓度的阿霉素或表阿霉素药代动力学评估可能无法完全阐明这两种药物之间的差异。这两种化合物都能与红细胞结合，它们与血红蛋白的不同结合可能会影响它们在体内的分布。本研究的目的是比较阿霉素和表阿霉素的药代动力学和代谢，基于血浆浓度、与血细胞的关联量以及单次和多次剂量注射后胆汁和尿液中未改变药物和代谢物的同步监测。心脏中肌浆网Ca2+ATP酶的水平也被测量作为心脏毒性的生物标志物。雄性Sprague-Dawley大鼠在平行设计中接受阿霉素或表阿霉素的多次剂量治疗（每周4 mg kg(-1)）或单次剂量注射（20 mg kg(-1)）。在多次剂量方案和单次剂量注射后，定期收集血液、尿液和胆汁样本，在每个实验结束时取出心脏。测定血浆、血细胞、胆汁和尿液样本中每种药物的浓度，并通过根据室分析将血浆和胆汁数据同时曲线拟合，估计药代动力学参数和常数。根据非室分析分析了与血细胞相关的药物浓度。胆汁和尿液样本提供了体内的代谢数据。通过Western印迹测定的心脏中Ca2+ATP酶的水平被用作与动力学数据相关的毒效动力参数。多次剂量方案减少了两种药物的总血浆清除率，并增加了血浆浓度-时间曲线下的面积。此外，随着每周剂量的增加，与血细胞相关的阿霉素曲线下面积增加，相关的平均停留时间（MRT）和表观分布体积（Vdss）稳步减少。与阿霉素相比，表阿霉素的平均停留时间和Vdss显著增加。代谢数据表明，醇和苷元代谢物的水平有显著差异。阿霉素醇和阿霉素苷元显著高于表阿霉素醇和表阿霉素苷元，而表阿霉素醇苷元高于阿霉素醇苷元。血细胞浓度-时间曲线下的面积与Ca2+ATP酶净强度的变化呈线性相关。本研究的结果表明，与血细胞相关的阿霉素和表阿霉素的动力学的重要性。与血细胞相关的阿霉素曲线下面积减少与生物标志物净强度减少之间的线性相关性证实，这两种化合物之间的差异与它们与血细胞的相互作用有关。这一观察结果以及观察到的代谢差异可能强调了血细胞在阿霉素和表阿霉素分布和代谢中的重要作用。

There is compelling in-vitro evidence that the evaluation of doxorubicin or epirubicin pharmacokinetics based solely on plasma concentration may not fully elucidate the differences between the two drugs. Both compounds bind to erythrocytes and their different binding to hemoglobin may influence their disposition in the body. The purpose of the present study was to compare the pharmacokinetics and metabolism of doxorubicin and epirubicin based on the plasma concentration, amount associated with blood cells and simultaneous monitoring of biliary and urinary elimination of unchanged drug and metabolites after single- and multiple-dose injections. The level of sarcoplasmic reticulum Ca2+ATPase in the heart was also measured as a biomarker of cardiotoxicity. Male Sprague-Dawley rats were treated in a parallel design with doxorubicin or epirubicin on a multiple-dosing basis (4 mg kg(-1) per week) or as a single dose injection (20 mg kg(-1)). Blood, urine and bile samples were collected periodically after each dose in the multiple-dosing regimen and the single dose injection, and at the end of each experiment the hearts were removed. The concentrations of each drug in plasma, blood cells, bile and urine samples were determined, and by simultaneous curve-fitting of plasma and bile data according to compartmental analysis, the pharmacokinetic parameters and constants were estimated. The concentration of drug associated with blood cells was analyzed according to non-compartmental analysis. The bile and urine samples provided the in-vivo metabolic data. The level of Ca2+ATPase in the heart, determined by Western blotting, was used as the toxicodynamic parameterto correlate with the kinetic data. Multiple-dosing regimens reduced the total plasma clearance and increased the area under the plasma concentration-time curve of both drugs. Also, the area under the curve of doxorubicin associated with blood cells increased with the weekly doses, and the related mean residence time (MRT) and apparent volume of distribution (Vdss) were steadily reduced. In contrast to doxorubicin, the mean residence time and Vdss of epirubicin increased significantly. Metabolic data indicated significant differences in the level of alcohol and aglycones metabolites. Doxorubicinol and doxorubicin aglycones were significantly greater than epirubicinol and epirubicin aglycone, whereas epirubicinol aglycone was greater than doxorubicinol aglycone. The area under the blood cells concentration-time curve correlated linearly with the changes in Ca2+ATPase net intensity. The results of this study demonstrate the importance of the kinetics of epirubicin and doxorubicin associated with blood cells. Linear correlation between the reduction of net intensity of the biomarker with the area under the curve of doxorubicin associated with blood cells confirms that the differences between the two compounds are related to their interaction with blood cells. This observation together with the observed differences in metabolism may underline a significant role for blood cells in distribution and metabolism of doxorubicin and epirubicin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

表柔比星（4'-表阿霉素；I）和阿霉素（11）的药代动力学在4名晚期癌症患者中进行了研究，这些患者通过静脉注射50毫克/平方米的剂量。药物衰减是三相的，具有长期终端半衰期。I的代谢物，表柔比星酚（13-二氢-4'-表阿霉素；III）的血浆和血液水平低于I。I和11的葡萄糖苷酸也存在于血浆、胆汁和尿液中。I的血浆清除率始终高于III的相应参数，平均滞留时间较短。此外，II的消除也快于阿霉素酚。在最初的诱导期之后，I的浓度在全血中高于血浆。血液清除率低于血浆清除率；如果在药代动力学分析中使用血液浓度数据，稳态下的分布体积较低。血液和血浆的平均滞留时间相似。即使在胆红素水平未改变的情况下，也观察到肝转移患者的清除参数有统计学意义的降低。

The pharmacokinetics of epirubicin (4' epidoxorubicin; I), and doxorubicin (11) following intravenous bolus injection of 50 mg/sq m, were investigated in 4 advanced cancer patients. Drug decay is triphasic, with long terminal half life. Plasma and blood levels of I metabolite, epirubicinol (13 dihydro 4' epidoxorubicin; III), are lower than those of 1. Glucuronides of I and 11 are also present in plasma, bile and urine. Plasma clearance of I is consistently higher and mean residence time lower than the corresponding III parameters. In addition, elimination of II was also faster than that of doxorubicinol. After an initial induction period, I concentration is higher in whole blood than in plasma. Blood clearance is lower than plasma clearance; volume of distribution at steady state is lower if blood concentration data are used in the pharmacokinetic analysis. Mean residence time is similar in blood and plasma. A statistically significant reduction of clearance parameters is observed in patients with liver metastases, even in the absence of altered bilirubin levels.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 肝毒性

血清转氨酶升高发生在多达40%的接受多柔比星治疗的病人中，但升高通常是无症状的且短暂的，即使在继续治疗的情况下也能解决。然而，已经有多柔比星导致急性肝损伤、症状和黄疸的报道，罕见情况下，表柔比星和依达鲁比星也有类似报道。在大多数情况下，患者正在接受多种抗癌化疗药物，认为蒽醌类抗生素增强了其他药物（如环磷酰胺、甲氨蝶呤或巯嘌呤）的毒性。联合抗肿瘤方案可能导致门静脉阻塞综合征，但多柔比星、表柔比星和依达鲁比星在此结果中的作用常常不清楚。瓦鲁比星在膀胱内局部给药（膀胱内给药）并且系统吸收很少，在治疗期间尚未与血清酶升高或临床上明显的肝损伤相关联。 多柔比星导致临床上明显肝损伤的可能性评分：B（可能是临床上明显肝损伤的原因）。 表柔比星和依达鲁比星的可能性评分：E*（未证实但怀疑是临床上明显肝损伤的原因）。 瓦鲁比星的可能性评分：E（不太可能是临床上明显肝损伤的原因）。

Serum aminotransferase elevations occur in up to 40% of patients on doxorubicin therapy, but elevations are generally asymptomatic and transient, resolving even with continuation of therapy. However, instances of acute liver injury with symptoms and jaundice have been reported with doxorubicin and rarely also with epirubicin and idarubicin. In most instances, multiple cancer chemotherapeutic agents were being administered and the anthracite antibiotic was believed to enhance the toxicity of the other agents (such as cyclosphosphamide, methotrexate or mercaptopurine). Combination antineoplastic regimens can cause sinusoidal obstruction syndrome, but the role of doxorubicin, epirubicin and idarubicin in this outcome is often not clear. Valrubicin is administered locally in the bladder (intravesical) and has little systemic absorption and has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury. Likehood score (doxorubicin): B (likely cause of clinically apparent liver injury). Likehood score (epirubicin and idarubicin): E* (unproven but suspected cause of clinically apparent liver injury). Likehood score (valrubicin): E (unlikely cause of clinically apparent liver injury).

来源:LiverTox

毒理性

• 相互作用

盐酸表柔比星配方中存在的甲基对羟基苯甲酸酯通过破坏表柔比星与其他成分之间的键合力，从而提高溶解速率。/盐酸表柔比星/

The methylparaben present in the epirubicin HCl formulation enhances the dissolution rate by disrupting bonding between epirubicin & other components. /Epirubicin HCl/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

柔红霉素的白细胞减少和/或血小板减少作用可能会在与导致同样效果的药物（如引起血液紊乱的药物）同时或反复治疗时增加；在这些情况下，柔红霉素的剂量应根据血细胞计数来确定。

Lleukopenic and/thrombocytopenic effects of epirubicin may be increased with concurrent or recurrent therapy if these medications /blood dyscrasia-causing medications/ cause the same effects; dosage of epirubicin should be based on blood counts in these cases.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

关于放疗和Ellence（依托泊苷）联合应用的数据较少。在含有Ellence的CEF-120或FEC-100化疗方案的辅助试验中，乳房放疗推迟到化疗完成后进行。这种做法与文献中发布的资料相比，并未明显增加局部乳腺癌复发的风险。少数患者在放疗的同时接受了以Ellence为基础的化疗，但为了防止潜在的毒性重叠，化疗被中断。使用Ellence进行放疗可能会使组织对放疗的细胞毒性作用更加敏感。在之前的放疗之后给予Ellence可能会在照射部位诱导出炎症回忆反应。

There are few data regarding the coadministration of radiation therapy and Ellence. In adjuvant trials of Ellence-containing CEF-120 or FEC-100 chemotherapies, breast irradiation was delayed until after chemotherapy was completed. This practice resulted in no apparent increase in local breast cancer recurrence relative to published accounts in the literature. A small number of patients received Ellence-based chemotherapy concomitantly with radiation therapy but had chemotherapy interrupted in order to avoid potential overlapping toxicities. It is likely that use of Ellence with radiotherapy may sensitize tissues to the cytotoxic actions of irradiation. Administration of Ellence after previous radiation therapy may induce an inflammatory recall reaction at the site of the irradiation.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

不要将表柔比星与其他具有心脏毒性的药物联合使用，除非密切监测患者的心脏功能。在停止使用其他具有心脏毒性的药物（尤其是半衰期较长的药物，如曲妥珠单抗）后接受表柔比星治疗的患者，也可能会增加发生心脏毒性的风险。与可能导致心力衰竭的其他心脏活性化合物（例如，钙通道阻滞剂）同时使用Ellence时，需要在整个治疗过程中密切监测心脏功能。

Do not administer epirubicin in combination with other cardiotoxic agents unless the patient's cardiac function is closely monitored. Patients receiving epirubicin after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity. Concomitant use of Ellence with other cardioactive compounds that could cause heart failure (e.g., calcium channel blockers), requires close monitoring of cardiac function throughout treatment.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...研究了/蒽环类抗生素/多柔比星（1）、4'表多柔比星（表柔比星；II）和柔红霉素（道诺霉素；III）在患者体内的血浆和组织分布。通过液相色谱法测定了I和II及其13-羟基代谢物的血浆水平，以及III的血浆水平。得出结论，这3种药物的血浆动力学相似，I和II的组织摄取几乎相同。肿瘤组织对药物的浓缩程度最高，而脂肪组织的浓度最低。

... The plasma and tissue distribution of /anthracyline antibiotics/ doxorubicin (1), 4' epidoxorubicin (epirubicin; II) and daunorubicin (daunomycin; III) were studied in patients. Plasma levels of I and II and their 13 hydroxy metabolites were determined by LC, as were plasma levels of III. It was concluded that plasma kinetics for the 3 drugs were similar, and that tissue uptake for I and II were virtually the same. Tumor tissue concentrated the drugs to the greatest extent, while adipose tissue had the lowest concentrations.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...对含有表柔比星盐酸盐（I）的卵白蛋白微球的制备和体内外评价进行了详细描述，在大鼠单次静脉给药后研究了I的药代动力学，并在携带艾利希腹水癌的小鼠和携带沃克肉瘤的大鼠中进行了疗效研究。药物在体外的释放动力学部分符合一级反应，也符合从基质扩散的模型。大鼠血清、心脏和肺部的药代动力学可以用两室开放模型的方程来描述。计算出的药代动力学参数表明，有可能通过肺部提高I的选择性捕获。在动物疗效研究中，I增加了所有处理组的存活时间。研究结果表明，I微球可能实现器官靶向。

... The preparation and in vitro and in vivo evaluation of egg albumin microspheres containing epirubicin hydrochloride (I) are /detailed/, I pharmacokinetics were studied in rats following single intravenous doses and efficacy studies were carried out in mice with Ehrlich ascites carcinoma and in rats with Walker carcinoma. The kinetics of in vitro release of the drug complied partially with first order as well as with a diffusion model from a matrix. The pharmacokinetics in serum, heart and lungs of rats could be described by the equation of the 2 compartment open model. The pharmacokinetic parameters calculated suggest the possibility of improving the selective entrapment of I by the lungs. In the animal efficacy studies I increased the survival times in all treated groups. It was concluded that the data suggest the possibility of organ targeting of I microspheres.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

/MILK/ 表柔比星在大鼠围产期和产后期间，以0.50 mg/kg/天的剂量给药时，会被排入乳汁中。目前尚不清楚该药物是否会被排入人类乳汁中。

/MILK/ Epirubicin was excreted into the milk of rats treated with 0.50 mg/kg/day of epirubicin during peri- and postnatal periods. It is not known whether this drug is excreted in human milk.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

静脉给药后，表柔比星迅速广泛地分布到组织中。表柔比星与血浆蛋白的结合率，主要是白蛋白，约为77%，且不受药物浓度的影响。表柔比星似乎也会在红细胞中浓缩；全血中的浓度大约是血浆中的两倍。

Following intravenous administration, epirubicin is rapidly and widely distributed into the tissues. Binding of epirubicin to plasma proteins, predominantly albumin, is about 77% and is not affected by drug concentration. Epirubicin also appears to concentrate in red blood cells; whole blood concentrations are approximately twice those of plasma.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• STABLE NANOCOMPOSITION COMPRISING EPIRUBICIN, PROCESS FOR THE PREPARATION THEREOF, ITS USE AND PHARMACEUTICAL COMPOSITIONS CONTAINING IT
  申请人：BORBÉLY János

  公开号：US20140296173A1

  公开（公告）日：2014-10-02

  A nanoparticulate composition is disclosed for the targeted therapeutic treatment of tumours. The stable self assembled nanocomposition according to the invention comprises (i) a carrier and targeting system comprising an optionally modified polyanion, and optionally a polycation, which may also be modified; at least one targeting agent which is linked to either the polycation/modified polycation or the polyanion/modified polyanion, or both; (ii) an active compound selected from the group of epirubicin and its pharmaceutically acceptable salts, especially hydrochloride; and optionally (iii) at least one complexing agent, metal ion and stabilizer/formulating agent. The invention furthermore relates to a process for the preparation of the above-mentioned composition, the therapeutic uses thereof, and pharmaceutical compositions containing the nanocomposition according to the invention.

  本发明公开了一种用于针对性治疗肿瘤的纳米颗粒组合物。根据本发明，稳定的自组装纳米组合物包括（i）载体和靶向系统，包括可选择修改的聚阴离子和可选择修改的聚阳离子，至少一种靶向剂连接到聚阳离子/修改聚阳离子或聚阴离子/修改聚阴离子中的一种或两种；（ii）从表儿霉素及其药学上可接受的盐中选择的活性化合物，特别是盐酸盐；以及可选的（iii）至少一种络合剂、金属离子和稳定剂/制剂剂。本发明还涉及上述组合物的制备方法、其治疗用途以及含有根据本发明的纳米组合物的制药组合物。
• SULFOMALEIMIDE-BASED LINKERS AND CORRESPONDING CONJUGATES
  申请人：PIERRE FABRE MEDICAMENT

  公开号：US20220023438A1

  公开（公告）日：2022-01-27

  The present invention relates to a linker of the following formula (I) or a salt thereof: (I). The present invention relates to a linker-drug conjugate of the following formula (II) or a salt thereof: (II). The present invention relates also to a binding unit-drug corrugate, such as an antibody-drug conjugate, of the following formula (III) or (IV) or a salt thereof: (III), (IV), as well as a pharmaceutical composition comprising such a binding unit-drug corrugate and its use in the treatment of cancer.