芜地溴铵 | 869185-19-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 芜地溴铵
• 英文名称: Umeclidinium
• 英文别名: diphenyl-[1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-4-yl]methanol
• CAS: 869185-19-3
• 化学式: C29H34NO2+
• 分子量: 428.6
• InChiKey: FVTWTVQXNAJTQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

体外数据显示，umeclidinium主要通过细胞色素P450 2D6（CYP2D6）酶代谢，并且是P-糖蛋白（P-gp）转运体的底物。umeclidinium的主要代谢途径是氧化（羟基化，脱烷基化）随后进行结合（例如，葡萄糖苷酸化），产生一系列代谢物，这些代谢物的药理活性降低或尚未确定。代谢物的系统性暴露较低。

In vitro data showed that umeclidinium is primarily metabolized by the enzyme cytochrome P450 2D6 (CYP2D6) and is a substrate for the P-glycoprotein (P-gp) transporter. The primary metabolic routes for umeclidinium are oxidative (hydroxylation, Odealkylation) followed by conjugation (e.g., glucuronidation), resulting in a range of metabolites with either reduced pharmacological activity or for which the pharmacological activity has not been established. Systemic exposure to the metabolites is low.

来源:DrugBank

毒理性

• 在妊娠和哺乳期间的影响

乳糖酶缺乏或乳糖不耐受是一种遗传性代谢紊乱，当小肠乳糖酶活性降低时发生，导致未被消化的乳糖进入大肠。

◉ Summary of Use during Lactation:Although no published data exist on the use of umeclidinium during breastfeeding, it produces low systemic maternal serum levels and any drug in breastmilk are not likely to be absorbed by the infant. The risk to the breastfed infant of maternal umeclidinium inhalation is small. Combination products such as Anoro Ellipta are likely to be acceptable for similar reasons. ◉ 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

89%

89%

来源:DrugBank

吸收、分配和排泄

• 吸收

Cmax出现在5到15分钟内，稳态浓度在14天内到达，累积了1.8倍。

Cmax occurred at 5 to 15 minutes, with steady state concentrations arriving in 14 days with 1.8-fold accumulation.

来源:DrugBank

吸收、分配和排泄

• 消除途径

静脉注射放射性标记的umeclidinium后，质量平衡显示58%的放射性标记在粪便中，22%在尿液中。

Following intravenous dosing with radiolabeled umeclidinium, mass balance showed 58% of the radiolabel in the feces and 22% in the urine.

来源:DrugBank

吸收、分配和排泄

• 分布容积

平均分布容积为86升。

Mean volume of distribution was 86 L.

来源:DrugBank

文献信息

• Muscarinic Acetylcholine Receptor Antagonists
  申请人：Laine Damane I.

  公开号：US20090124653A1

  公开（公告）日：2009-05-14

  Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided.

  本文提供了毒蕈碱乙酰胆碱受体拮抗剂及其使用方法。
• COMBINATIONS OF A MUSCARINIC RECEPTOR ANTAGONIST AND A BETA-2 ADRENORECEPTOR AGONIST
  申请人：Baker Darrell

  公开号：US20120309725A1

  公开（公告）日：2012-12-06

  Novel combinations of a muscarinic acetylcholine receptor antagonist and a beta 2 agonist for inhaled administration via the nose or mouth, and methods of using them are provided.

  本发明提供了一种新的组合，包括毒蕈碱乙酰胆碱受体拮抗剂和β2激动剂，用于通过鼻子或口腔进行吸入给药，并提供了使用它们的方法。
• Novel Combination of Therapeutic Agents
  申请人：Crater Glenn

  公开号：US20140113888A1

  公开（公告）日：2014-04-24

  The present invention is directed to the combination of a muscarinic receptor antagonist and a corticosteroid, and the use of said combination in treating diseases mediated via the M 3 muscarinic acetylcholine receptor and/or the glucocorticoid receptor, such as asthma.

  本发明涉及一种肌肉型乙酰胆碱受体拮抗剂和皮质类固醇的组合，以及利用该组合治疗通过M3肌肉型乙酰胆碱受体和/或糖皮质激素受体介导的疾病，例如哮喘。
• Dry Powder Inhaler Compositions
  申请人：GLAXO GROUP LIMITED

  公开号：US20140116434A1

  公开（公告）日：2014-05-01

  Dry powder inhalers comprising a muscarinic acetylcholine receptor antagonist and optionally a beta 2 agonist and/or a corticosteroid for use in the treatment of inflammatory or respiratory tract diseases, such as asthma or COPD.

  干粉吸入器包括一种肌动蛋白乙酰胆碱受体拮抗剂，可选择地包括一种β2激动剂和/或皮质类固醇，用于治疗炎症或呼吸道疾病，如哮喘或COPD。
• COMBINATION OF UMECLIDINIUM, FLUTICASONE PROPIONATE AND SALMETEROL XINAFOATE FOR USE IN THE TREATMENT OF INFLAMMATORY OR RESPIRATORY TRACT DISEASES
  申请人：GLAXO GROUP LIMITED

  公开号：US20150313841A1

  公开（公告）日：2015-11-05

  The present invention is directed to pharmaceutical combination products comprising a muscarinic acetylcholine receptor antagonist, fluticasone propionate and salmeterol xinafoate, and to their use in the treatment of inflammatory or respiratory tract diseases.

  本发明涉及药物组合产品，包括毒蕈碱乙酰胆碱受体拮抗剂、氟替卡松丙酸酯和沙美特罗西那福酯，并且涉及它们在治疗炎症或呼吸道疾病中的用途。