伊达比星-简介
【药品名称】 伊达比星
【英文名称】 Idarubicin
【中文别名】4-去甲氧基柔红霉素、埃得霉素、去甲柔毛霉素、去甲氧柔红霉素、柔吡星、依达比星、依达吡星
【英文别名】Demethoxydaunorubicin、Idamycin
【性状】本品的盐酸盐为鲜橙色结晶，m.p.172～l74。
类别 ：西医药物
【伊达比星-动力学】   
肾脏
本品属二室或三室开放模型。10～15mg／平方米快速静注，t1/2β为16分钟(9～36分钟)，t1/2α为19小时(10.5～34.7小时)，Vd15.33～17.05L／平方米。
本品在肝脏代谢为4-脱甲氧基-13-二氢柔红霉素(Ida酚)，作用与本品相似，因此本品的细胞毒作用也可能与Ida酚有关。
口服生物利用度为28％(4～89％)。Tpk2～4小时，t1/2β16.6小时。口服本品后，Ida酚有较高的AUC，表明很可能存在首过效应。本品及Ida酚主要经胆汁分泌。
静脉和口服给药后，本品的肾脏消除分别为2.3％～6.5％和0.4％～2.4％。
【伊达比星-适应症】   
急性淋巴细胞性白血病和急性非淋巴细胞性白血病。
成人急性非淋巴细胞性白血病的诱导缓解，复发，难治病人的诱导缓解。
成人和儿童急性淋巴细胞性白血病的二线治疗，还可用于综合化疗方案。
【伊达比星-用法用量】   
骨髓抑制
通常每日7～8mg／平方米，静脉注射3～5天为1疗程。
也可口服每日15～30mg/平方米，三天为1疗程。
本品可能引起骨髓抑制，因此治疗过程要密切注意血象变化。
并由于它的心脏毒性，还要监测心脏功能，及肝肾功能。若胆红素和肌酸酐值＞2mg％应暂停治疗。

【伊达比星-不良反应】   
淋巴细胞
1．心脏毒性可有急性心律失常(室上性及室性心动过速、室性及房性早搏、房颤)、心电图异常(非特异性STT波改变、T波平坦、右半支及左前半支传导阻滞)及慢性心肌病。
2．骨髓抑制本品的骨髓抑制作用呈剂量限制性。表现为淋巴细胞减少和血小板减少，或出现贫血。白细胞最低点一般出现在8～29天，21至35天恢复正常。血小板抑制不常见，可在10～15天降到最低，22～28天恢复正常。胃肠道反应较常见的有恶心、呕吐、腹泻和胃炎。
有报道，本品单独静注或口服(40～45mg/平方米×3d)时，腹泻发生率分别为11％～12％和10％～38％。胃炎与给药剂量有关，单用Ida约有9％的病人发生胃炎，甚至有胃穿孔者。可逆性脱发，单独静注时，秃光症的发生率为24％～33％。
【伊达比星-注意事项】   
严惩肝肾功能不全，感染未得到控制，曾接受药物或放射治疗引起骨髓抑制，心脏病患者。妊娠及哺乳妇女。老年人、高尿酸摁症患者及全身性感染病人慎用。治疗过程中或药几周内，可能发生心毒性反应，即潜在性、致肌病，表现为持续性的QRS低电压，收缩新时期延长(PEP/LVET)，左心室射血分数减低。出现这些反应时可用洋地黄、利尿剂、制钠盐及臣床休息等措施。
心脏
治疗过程中应注意监测心脏功能。纵隔心包区有过治疗，用过潜在性心脏毒性药物。伴有其它疾病（如贫血、骨髓抑制、感染、心肌炎）者。心脏毒性反应则更大。本药是骨髓抑制剂，除非大于弊的情况下，否则由于先前药物治疗或放疗引起骨髓抑制的病人不可使用本药。治疗剂量道德对白细胞有抑制作用，治疗时应注意监测粒性白细胞，红细胞和血小板。在治疗前和治疗中应监测肝和肾功能（血清胆红素、肌酐），如果胆红素或血清肌酐水平的1.2-2MG%，剂量应该减半，胆红或血清肌酐超过2MG%出不予给药。
注意血中尿酸的浓度。静脉注射外渗会引起严惩的局部组织坏死，注射部位如果有蛰伤或灼热感，应马上停止，选用另一个静脉注射。对妊娠和哺乳的影响没有方献报道本药会影响人的生育能力或引起畸胎，但对大鼠能致畸，具有胚胎毒性。生育期的妇女应该避，如用于孕妇或病人在治疗过程中怀孕，应告诉病人本药对胎儿有潜在的危害，用本药治疗的妇女不能哺乳。
【伊达比星-制剂】   
用乳糖配制的注射剂，每小瓶含本品5mg；10mg

【原产地英文商品名】IDARUBICIN HCL -5mg/5ml,5ml/Vial
【原产地英文药品名】IDARUBICIN HCL-5mg/5ml,5ml/Vial
【中文参考商品译名】盐酸伊达比星-5毫克/5毫升,5毫升/瓶
【中文参考药品译名】
提示：以下产品不同的规格和不同的价格，购买时请以电话咨询为准
·盐酸伊达比星-5毫克/5毫升,5毫升/瓶
·盐酸伊达比星-20毫克/20毫升,20毫升/瓶
·盐酸伊达比星-10毫克/10毫升,10毫升/瓶
·伊达比星-1毫克/毫升, 5毫升/瓶
·伊达比星-1毫克/毫升, 20毫升/瓶
【中文参考化合物名称】去甲氧基柔红霉素

Generic Name: idarubicin hydrochloride
Dosage Form: Injection

FOR INTRAVENOUS USE ONLY

Warnings
Idamycin PFS Injection should be given slowly into a freely flowing intravenous infusion. It must never be given intramuscularly or subcutaneously. Severe local tissue necrosis can occur if there is extravasation during administration.
As is the case with other anthracyclines the use of Idamycin PFS can cause myocardial toxicity leading to congestive heart failure. Cardiac toxicity is more common in patients who have received prior anthracyclines or who have pre-existing cardiac disease.
As is usual with antileukemic agents, severe myelosuppression occurs when Idamycin PFS is used at effective therapeutic doses.
It is recommended that Idamycin PFS be administered only under the supervision of a physician who is experienced in leukemia chemotherapy and in facilities with laboratory and supportive resources adequate to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The physician and institution must be capable of responding rapidly and completely to severe hemorrhagic conditions and/or overwhelming infection.
Dosage should be reduced in patients with impaired hepatic or renal function. (See DOSAGE AND ADMINISTRATION.)
Idamycin PFS - Clinical Pharmacology
Mechanism of Action
Idarubicin hydrochloride is a DNA-intercalating analog of daunorubicin which has an inhibitory effect on nucleic acid synthesis and interacts with the enzyme topoisomerase II. The absence of a methoxy group at position 4 of the anthracycline structure gives the compound a high lipophilicity which results in an increased rate of cellular uptake compared with other anthracyclines.

Pharmacokinetics
General Pharmacokinetics
Pharmacokinetic studies have been performed in adult leukemia patients with normal renal and hepatic function following intravenous administration of 10 to 12 mg/m2 of idarubicin daily for 3 to 4 days as a single agent or combined with cytarabine. The plasma concentrations of idarubicin are best described by a two or three compartment open model. The elimination rate of idarubicin from plasma is slow with an estimated mean terminal half-life of 22 hours (range, 4 to 48 hours) when used as a single agent and 20 hours (range, 7 to 38 hours) when used in combination with cytarabine. The elimination of the primary active metabolite, idarubicinol, is considerably slower than that of the parent drug with an estimated mean terminal half-life that exceeds 45 hours; hence, its plasma levels are sustained for a period greater than 8 days.

Distribution
The disposition profile shows a rapid distributive phase with a very high volume of distribution presumably reflecting extensive tissue binding. Studies of cellular (nucleated blood and bone marrow cells) drug concentrations in leukemia patients have shown that peak cellular idarubicin concentrations are reached a few minutes after injection. Concentrations of idarubicin and idarubicinol in nucleated blood and bone marrow cells are more than a hundred times the plasma concentrations. Idarubicin disappearance rates in plasma and cells were comparable with a terminal half-life of about 15 hours. The terminal half-life of idarubicinol in cells was about 72 hours. The extent of drug and metabolite accumulation predicted in leukemia patients for Days 2 and 3 of dosing, based on the mean plasma levels and half-life obtained after the first dose, is 1.7- and 2.3-fold, respectively, and suggests no change in kinetics following a daily × 3 regimen. The percentages of idarubicin and idarubicinol bound to human plasma proteins averaged 97% and 94%, respectively, at concentrations similar to maximum plasma levels obtained in the pharmacokinetic studies. The binding is concentration independent. The plasma clearance is twice the expected hepatic plasma flow indicating extensive extrahepatic metabolism.

Metabolism
The primary active metabolite formed is idarubicinol. As idarubicinol has cytotoxic activity, it presumably contributes to the effects of idarubicin.

Elimination
The drug is eliminated predominately by biliary and to a lesser extent by renal excretion, mostly in the form of idarubicinol.

Pharmacokinetics in Special Populations
Pediatric Patients
Idarubicin studies in pediatric leukemia patients, at doses of 4.2 to 13.3 mg/m2/day × 3, suggest dose independent kinetics. There is no difference between the half-lives of the drug following daily × 3 or weekly × 3 administration. Cerebrospinal fluid (CSF) levels of idarubicin and idarubicinol were measured in pediatric leukemia patients treated intravenously. Idarubicin was detected in 2 of 21 CSF samples (0.14 and 1.57 ng/mL), while idarubicinol was detected in 20 of these 21 CSF samples obtained 18 to 30 hours after dosing (mean = 0.51 ng/mL; range, 0.22 to 1.05 ng/mL). The clinical relevance of these findings is unknown.
Hepatic and Renal Impairment
The pharmacokinetics of idarubicin have not been evaluated in leukemia patients with hepatic impairment. It is expected that in patients with moderate or severe hepatic dysfunction, the metabolism of idarubicin may be impaired and lead to higher systemic drug levels. The disposition of idarubicin may be also affected by renal impairment. Therefore, a dose reduction should be considered in patients with hepatic and/or renal impairment (see DOSAGE AND ADMINISTRATION).