Ambisome | 1397-89-3

• 物质功能分类: 原料药 - 抗生素类药物 - 多烯类药
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Ambisome
• 英文别名: 33-(4-amino-3,5-dihydroxy-6-methyloxan-2-yl)oxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid
• CAS: 1397-89-3
• 化学式: C₄₇H₇₃NO₁₇
• 分子量: 924.1
• InChiKey: APKFDSVGJQXUKY-UHFFFAOYSA-N

物化性质

• 熔点：
  >170°C
• 比旋光度：
  D24 +333° (acidic DMF); -33.6° (0.1N methanolic HCl)
• 沸点：
  804.34°C (rough estimate)
• 密度：
  1.34
• 溶解度：
  无菌水：20 mg/mL作为储存液。储存液应储存在−20°C。在37℃下稳定保存3天。
• 颜色/状态：
  Deep yellow prisms or needles from n,n-dimethylformamide
• 气味：
  ODORLESS OR PRACTICALLY SO
• 稳定性/保质期：

  如果按照规格正确使用和储存，则不会分解，未有已知危险反应。请避免接触氧化物。

• 旋光度：
  Specific optical rotation at 24 °C/D: +333 deg (acidic N,N-dimethylformamide); -33.6 deg (0.1 N methanolic hydrochloric acid)
• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides/.

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  65
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  320
• 氢给体数：
  12
• 氢受体数：
  18

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：尽管没有关于两性霉素B乳汁排出的信息，但由于它高度与蛋白质结合，分子量大，几乎不被口服吸收，并且已经直接用于婴儿口腔；因此，大多数审阅者认为在哺乳期母亲中使用是可以接受的。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Although no information exists on the milk excretion of amphotericin B, it is highly protein bound, has a large molecular weight, is virtually unabsorbed orally and has been use directly in the mouths of infants; therefore, most reviewers consider it acceptable to use in nursing mothers. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

由于肾毒性作用可能叠加，应尽可能避免同时或连续使用两性霉素B和其他具有类似毒性潜力的药物（例如，氨基糖苷类抗生素、卡泊霉素、粘菌素、顺铂、环孢素、甲氧氟烷、戊烷脒、多粘菌素B、万古霉素）。

Since nephrotoxic effects may be additive, the concurrent or sequential use of amphotericin B and other drugs with similar toxic potentials (eg, aminoglycosides, capreomycin, colistill, cisplatin, cyclosporine, methoxyflurane, pentamidine, polymyxin B, vancomycin) should be avoided, if possible.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

据报道，皮质类固醇可能会增强两性霉素B引起的钾流失，除非有必要控制对两性霉素B的不良反应，否则不应同时使用。

Corticosteroids reportedly may enhance the potassium depletion caused by amphotericin B and should not be used concomitantly unless necessary to control adverse reactions to amphotericin B.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

抗肿瘤药物（例如，美克洛塞）可能会增加接受两性霉素B治疗的患者出现肾毒性、支气管痉挛和低血压的风险，因此此类联合治疗应非常谨慎使用。

Antineoplastic agents (eg, mechlorethamine) may enhance the potential for renal toxicity, bronchospasm, and hypotension in patients receiving amphotericin B and such concomitant therapy should be used only with great caution.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在一项随机双盲研究中，评估了常规静脉注射两性霉素B和两性霉素B胆固醇硫酸盐复合物在发热中性粒细胞减少症患者中的使用情况，这些患者的基线血清肌酐浓度正常。研究中，肾脏毒性（定义为血清肌酐从基线翻倍或增加1 mg/dL或更多，或从基线计算出的肌酐清除率下降50%或更多）的发生率，在接受两性霉素B胆固醇硫酸盐复合物并同时使用环孢素或他克莫司的成人和儿童患者中为31%，而接受常规两性霉素B并同时使用这些药物的成人和儿童患者中为68%。在没有接受环孢素或他克莫司治疗的成人和儿童患者中，接受两性霉素B胆固醇硫酸盐复合物的肾脏毒性发生率为8%，而接受常规两性霉素B的发生率为35%。

In a randomized, double-blind study that evaluated use of conventional IV amphotericin B and amphotericin B cholesteryl sulfate complex in febrile neutropenic patients with normal baseline serum creatinine concentrations, the incidence of renal toxicity (defined as a doubling or an increase of 1 mg/dL or more from baseline serum creatinine or a 50% or greater decrease from baseline in calculated creatinine clearance) was 31% in adults and pediatric patients who received amphotericin B cholesteryl sulfate complex concomitantly with cyclosporine or tacrolimus compared with 68% in those who received conventional amphotericin B concomitantly with these agents. In adults and pediatric patients who did not receive cyclosporine or tacrolimus therapy, the incidence of renal toxicity was 8% in those who received amphotericin B cholesteryl sulfate complex and 35% in those who received conventional amphotericin B.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

两性霉素B的药代动力学因药物是以传统两性霉素B（与去氧胆酸钠配方）、两性霉素B胆固醇硫酸盐复合物、两性霉素B脂质体复合物还是两性霉素B脂质体形式给药而有很大差异，一种两性霉素B制剂的药代动力学参数不应用来预测任何其他两性霉素B制剂的药代动力学。

The pharmacokinetics of amphotericin B vary substantially depending on whether the drug is administered as conventional amphotericin B (formulated with sodium desoxycholate), amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, or amphotericin B liposomal, and pharmacokinetic parameters reported for one amphotericin B formulation should not be used to predict the pharmacokinetics of any other amphotericin B formulation.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

两性霉素B从胃肠道吸收不良，必须通过胃肠道外给药来治疗全身性真菌感染。在一项研究中，静脉输注30毫克两性霉素B（在几小时内给药）后立即，平均血药峰浓度约为1微克/毫升；当剂量为50毫克时，平均血药峰浓度大约为2微克/毫升。输注后立即，血清中最多只能解释10%的两性霉素B剂量。当每天给予30毫克的剂量或每隔一天给予60毫克的剂量时，记录的平均最低血药浓度约为0.4微克/毫升。

Amphotericin B is poorly absorbed from the GI tract and must be given parenterally to treat systemic fungal infections. In one study, immediately after completion of iv infusion of 30 mg of amphotericin B (administered over a period of several hours), average peak serum concentrations were about 1 ug/ml; when the dose was 50 mg, average peak serum concentrations were approximately 2 ug/ml. Immediately after infusion, no more than 10% of the amphotericin B dose can be accounted for in serum. Average minimum serum concentrations (recorded just prior to the next drug infusion) of approximately 0.4 ug/ml have been reported when doses of 30 mg were given daily or when doses of 60 mg were given every other day.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄