Ipratropium | 60205-81-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: Ipratropium
• 英文别名: [(1S,5R)-8-methyl-8-propan-2-yl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate
• CAS: 60205-81-4
• 化学式: C20H30NO3+
• 分子量: 332.5
• InChiKey: OEXHQOGQTVQTAT-BZQJJPTISA-N

物化性质

• 溶解度：
  甲醇（微溶）、水（微溶）
• 物理描述：
  Solid
• 沸点：
  Decomposes at 230 ºC
• 熔点：
  230-232°C

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

异丙托溴铵在胃肠系统中通过细胞色素P-450同工酶的活性进行代谢。从口服给药剂量中，大约90%的剂量以原形排出。被吸收的部分通过酯水解部分代谢为不活跃的代谢物，包括托品酸和莨菪烷。

Ipratropium is metabolized in the gastrointestinal tract by the activity of the cytochrome P-450 isoenzymes. From the orally administered dose, about 90% of the dose is excreted unchanged. The absorbed portion is partially metabolized by ester hydrolysis to inactive metabolites, tropic acid and tropane.

来源:DrugBank

毒理性

• 肝毒性

与其他抗胆碱能药物一样，异丙托溴铵并未与肝酶升高或临床上明显的肝脏损伤发生关联。其安全性较高的一个主要原因是通过吸入器给药时其系统吸收较低。 关于抗胆碱能药物的安全性和潜在肝毒性的参考资料，在抗胆碱能药物概述部分之后给出。 药物类别：抗胆碱能药物

Like other anticholinergic agents, ipratropium has not been linked to episodes of liver enzyme elevations or clinically apparent liver injury. A major reason for its safety may relate to its low systemic absorption when administered by inhaler. References on the safety and potential hepatotoxicity of anticholinergics are given together after the Overview section on Anticholinergic Agents. Drug Class: Anticholinergic Agents

来源:LiverTox

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：尽管没有发表的数据关于使用异丙托溴铵，但其使用产生的母体血清水平微不足道，任何药物在乳汁中都不会被婴儿吸收。母亲吸入异丙托溴铵对哺乳婴儿的风险很小。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发表信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发表信息。

◉ Summary of Use during Lactation:Although no published data exist on the use of ipratropium, its use produces negligible maternal serum levels and any drug in breastmilk would not be absorbed by the infant. The risk to the breastfed infant of maternal ipratropium inhalation is small. ◉ 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

• 蛋白质结合

伊普罗托品的蛋白质结合非常低，因为循环中的伊普罗托品水平非常微小。结合状态仅占给药剂量的0-9%。

The protein binding of ipratropium is very low as the level of circulating ipratropium is very minimal. The bound state represents only from 0-9% of the administered dose.

来源:DrugBank

吸收、分配和排泄

• 吸收

异丙托溴铵是一种局部活性但吸收不良的药物。其在粘膜表面的吸收潜力较低，这与分子中5价氮原子上带电荷有关。尽管分子本身具有很大的局部有效性，但它不会产生可检测的血药水平或系统性效果。口服或吸入给药后，异丙托溴铵的血清水平非常低，仅相当于给药剂量的1-2%。这些低水平在1-2小时后达到峰值，并表现出很低的生物利用度，仅为2%。

Ipratropium is a topically active but poorly absorbed agent. The lack of absorption potential in the mucosal surfaces is associated with the presence of a charge in the 5-valent nitrogen. The molecule itself presents very large topic effectiveness however, it does not produce detectable blood levels nor systemic effects. Serum levels of ipratropium after oral or inhaled administration are very low, corresponding to only 1-2% of the administered dose. These low levels peak after 1-2 hours and it presents a low bioavailability of 2%.

来源:DrugBank

吸收、分配和排泄

• 消除途径

大约80-100%的给予的异丙托溴铵剂量通过尿液排出，少于20%的剂量通过粪便排出。从尿液中排出的部分几乎全部是未改变的药物。然而，当异丙托溴铵口服给药时，由于吸收率低，大部分剂量在粪便中回收，尿液中只发现极少量。

About 80-100% of the administered dose of ipratropium is excreted in the urine leaving less than 20% of the dose to be eliminated through the feces. From the urine eliminated portion, almost all the drug is found unchanged. However, when ipratropium is orally administered, due to its low absorption, most of the dose is recovered in the feces with a very minimal amount found in the urine.

来源:DrugBank

吸收、分配和排泄

• 分布容积

异丙托溴铵的分布容积为4.6 L/kg，因此，它被认为在组织中高度分布。

Ipratropium has a volume of distributions of 4.6 L/kg and hence, it is known to be highly distributed in the tissues.

来源:DrugBank

吸收、分配和排泄

• 清除

平均清除率为2.3升/分钟，肾清除率为0.9升/分钟。

The average clearance rate of ipratropium is of 2.3 L/min with a renal clearance of 0.9 L/min.

来源:DrugBank