amphotericin B | 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: amphotericin B
• 英文别名: AmB；3-Cyanobenzenemethanol；(1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,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: 924.093
• InChiKey: APKFDSVGJQXUKY-KKGHZKTASA-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

• 药物性肝损伤

复合物：两性霉素B

Compound:amphotericin b

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注解：较少的药物性肝损伤关注

DILI Annotation:Less-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重性等级：3

Severity Grade:3

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：警告和预防措施

Label Section:Warnings and precautions

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 用于研究药物诱导肝损伤的FDA批准药物标签，药物发现今日，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按在人类中发展药物诱导肝损伤风险排名的最大参考药物清单。药物发现今日2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

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于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）完成后，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。输注后即刻，血清中只能检测到不超过10%的两性霉素B剂量。当每天给予30毫克剂量或每隔一天给予60毫克剂量时，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

两性霉素B的分布信息有限，尽管分布显然是多室的。据报道，给予常规