(1S,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-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 | 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: (1S,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-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-PMWARXAXSA-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：

  Solids and solutions appear stable for long periods between pH 4 and 10 when stored at moderate temperature out of light and air.

• 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

• 肝毒性

多达20%的使用两性霉素的患者会出现轻度和短暂的肝酶升高。临床上明显的肝毒性很少见，但已经发表了一些确信的病例。肝脏损伤可能在开始治疗后的4到14天就出现，通常表现为肝细胞或混合模式的酶升高。大多数患者没有症状或黄疸。停止治疗后，恢复会很快发生。此外，尽管罕见，但已经报告了在开始使用两性霉素几天内出现的孤立但明显的胆红素血症案例，升高中大部分是直接（结合）胆红素部分。这些患者出现肉眼可见的黄疸，但没有全身症状，血清ALT或碱性磷酸酶水平升高的情况很少，没有明显肝损伤的证据。最后，已经罕见报道了在接受两性霉素的患者中出现急性胆汁淤积性肝炎伴黄疸的案例，但这些患者通常病情危重，并且接触了多种可能具有肝毒性的药物，因此将病因归咎于两性霉素的依据不强。

Mild and transient elevations in liver enzymes occur in up to 20% of patients receiving amphotericin. Clinically apparent hepatotoxicity is rare, but several convincing cases have been published. The liver injury arises as early as 4 to 14 days after starting therapy, typically with a hepatocellular or mixed pattern of enzyme elevation. Most patients have no symptoms or jaundice. Recovery occurs promptly upon stopping therapy. In addition, isolated but dramatic instances of hyperbilirubinemia arising within days of starting amphotericin have been reported with elevations largely in the direct (conjugated) bilirubin fraction. These patients become visually jaundiced but have no constitutional symptoms, minimal if any elevations in serum ALT or alkaline phosphatase levels, and no evidence of frank hepatic injury. Finally, rare instances of acute cholestatic hepatitis with jaundice have been reported in patients receiving amphotericin, but these patients have generally been critically ill and exposed to multiple potentially hepatotoxic agents, so that the attribution to amphotericin has been weak.

来源:LiverTox

毒理性

• 相互作用

由于肾毒性作用可能具有相加性，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、可利霉素、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)