(1R,4S,5'S,6R,6'R,8R,10E,13S,14E,16E,20R,21R,24S)-6'-[(2S)-butan-2-yl]-21,24-dihydroxy-12-[(2R,4S,6S)-5-[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (1R,4S,5'S,6R,6'R,8R,10E,13S,14E,16E,20R,21R,24S)-6'-[(2S)-butan-2-yl]-21,24-dihydroxy-12-[(2R,4S,6S)-5-[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one
• 化学式: C₄₈H₇₄O₁₄
• 分子量: 875.1
• InChiKey: AZSNMRSAGSSBNP-WKRCCXHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  62
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  170
• 氢给体数：
  3
• 氢受体数：
  14

ADMET

代谢

主要在肝脏。伊维菌素及其代谢物几乎全部通过粪便排泄，估计需要12天，给药剂量的不到1%通过尿液排泄。消除途径：伊维菌素在肝脏中代谢，伊维菌素及其代谢物几乎全部通过粪便排泄，估计需要12天，给药剂量的不到1%通过尿液排泄。半衰期：16小时（也有报道称22-28小时）。

Primarily hepatic. Ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1 % of the administered dose excreted in the urine. Route of Elimination: Ivermectin is metabolized in the liver, and ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose excreted in the urine. Half Life: 16 hours (also reported at 22-28 hours)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

伊维菌素选择性地与高亲和力地结合到无脊椎动物肌肉和微丝虫神经细胞中的谷氨酸门控氯离子通道。这种结合导致细胞膜对氯离子的通透性增加，进而导致细胞超极化，致使寄生虫瘫痪和死亡。伊维菌素还被认为是神经递质γ-氨基丁酸（GABA）的激动剂，从而干扰GABA介导的中枢神经系统（CNS）神经突触传递。伊维菌素还可能损害O. volvulus微丝虫的正常子宫内发育，并可能阻止妊娠雌虫子宫中的微丝虫释放。它具有低水溶性，广泛的非特异性结合。它打开了对GABA不敏感的氯通道，降低膜电阻，增加内向电导。

Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells of the microfilaria. This binding causes an increase in the permeability of the cell membrane to chloride ions and results in hyperpolarization of the cell, leading to paralysis and death of the parasite. Ivermectin also is believed to act as an agonist of the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting GABA-mediated central nervous system (CNS) neurosynaptic transmission. Ivermectin may also impair normal intrauterine development of O. volvulus microfilariae and may inhibit their release from the uteri of gravid female worms. It has low solubility in water and extensive non-specific binding. It opens GABA-insensitive chloride channels, reducing membrane resistance and increasing conductance inward. (T10)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

未列在IARC目录中。

Not listed by IARC.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

阿维菌素类具有神经毒性，并且对生殖和发育有影响。

Avermectins are neurotoxic and have reproductive and developmental effects. (L1826)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

伊维菌素吸收中等良好。高脂肪餐可提高吸收。

Ivermectin is moderately well absorbed. Improved absorption with high fat meal.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

阿维菌素会导致皮肤和眼睛刺激、中枢神经系统抑制（不协调、震颤、乏力、兴奋、瞳孔扩大、昏迷）、呕吐、惊厥和/或震颤，以及在高剂量下的呼吸衰竭。（L1826）不良反应包括肌肉或关节疼痛、头晕、发热、头痛、皮疹和心跳加速。

Avermectins cause irritation of skin and eyes, central nervous system depression (incoordination, tremors, lethargy, excitation, pupil dilation, coma), vomiting, convulsions and/or tremors, and respiratory failure at high doses. (L1826) Adverse effects include muscle or joint pain, dizziness, fever, headache, skin rash, fast heartbeat.

来源:Toxin and Toxin Target Database (T3DB)

文献信息

• Solid injectable veterinary implants comprising monocyclic lactone
  申请人：CEVA SANTE ANIMALE

  公开号：US11318156B2

  公开（公告）日：2022-05-03

  The present invention relates to an injectable implant comprising an effective amount of a macrocyclic lactone, or a salt thereof, and a bioresorbable polymer, and its use in preventing and/or treating parasites infestations in non human mammals, especially pets.

  本发明涉及一种由有效量的大环内酯或其盐和生物可吸收聚合物组成的可注射植入物，及其在预防和/或治疗非人类哺乳动物，尤其是宠物的寄生虫感染中的用途。
• COMPOSITION FOR TREATING WORMS INFESTATIONS
  申请人：Ceva Santé Animale

  公开号：EP3609470A1

  公开（公告）日：2020-02-19
• [EN] COMPOSITION FOR TREATING WORMS INFESTATIONS<br/>[FR] COMPOSITION POUR LE TRAITEMENT D'INFESTATIONS PAR DES VERS
  申请人：CEVA SANTE ANIMALE

  公开号：WO2018189314A1

  公开（公告）日：2018-10-18

  The present invention relates to an injectable implant comprising an effective amount of a macrocyclic lactone, or a salt thereof, and a bioresorbable polymer, and its use in preventing and/or treating parasites infestations in non human mammals, especially pets.
• [EN] ORAL DISSOLVABLE FILM AND METHOD OF MANUFACTURING AND USING THE SAME<br/>[FR] FILM SOLUBLE ORAL ET SON PROCÉDÉ DE FABRICATION ET D'UTILISATION
  申请人：CURE PHARMACEUTICAL HOLDING CORP

  公开号：WO2021138564A1

  公开（公告）日：2021-07-08

  The present invention provides for an oral dissolvable film and a method of manufacturing and using the same.
• [EN] ORAL FORMULATION OF IVERMECTIN AND USES THEREOF<br/>[FR] FORMULATION PAR VOIE ORALE D'IVERMECTINE ET UTILISATIONS
  申请人：[fr]SUBSTIPHARM

  公开号：WO2022200402A1

  公开（公告）日：2022-09-29

  L'invention a pour objet une formulation galénique, adaptée à une administration par voie orale, comprenant une enveloppe renfermant des mini formulations sous forme solide, ayant une taille inférieure à 4,5 mm, d'ivermectine micronisée; son procédé de préparation et ses utilisations.