(1'R,2R,3S,4'S,6S,8'R,10'Z,12'S,14'Z,16'Z,20'R,21'R,24'S)-2-cyclohexyl-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-3,11',13',22'-tetramethylspiro[2,3-dihydropyran-6,6'-3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene]-2'-one | 117704-25-3

• 物质功能分类: 原料药 - 抗寄生虫病药 - 抗蠕虫药
• 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: (1'R,2R,3S,4'S,6S,8'R,10'Z,12'S,14'Z,16'Z,20'R,21'R,24'S)-2-cyclohexyl-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-3,11',13',22'-tetramethylspiro[2,3-dihydropyran-6,6'-3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene]-2'-one
• CAS: 117704-25-3
• 化学式: C₅₀H₇₄O₁₄
• 分子量: 899.1
• InChiKey: QLFZZSKTJWDQOS-PCCBEZLYSA-N

物化性质

• 熔点：
  116-1190C
• 沸点：
  967.4±65.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于甲醇：
• LogP：
  4.39-4.43 at 25℃

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  64
• 可旋转键数：
  7
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  170
• 氢给体数：
  3
• 氢受体数：
  14

ADMET

代谢

以三氚标记的5位多拉菌素单次给药于Sprague-Dawley大鼠（2只雄性，以丙二醇:丙三醇为溶剂，通过灌胃给予5 mg/kg体重），一只比格犬（1只雌性，以芝麻油为溶剂，通过灌胃给予3.5 mg/kg体重）和牛（5只雄性，皮下给予0.2 mg/kg体重）。从各物种的肝脏和粪便以及牛的脂肪中鉴定出了以下代谢物... /未改变的多拉菌素、3"-O-去甲基多拉菌素、24-羟甲基多拉菌素和24-羟甲基-3"-O-去甲基多拉菌素。/

Doramectin labelled with tritium in the 5-position was administered as a single dose to Sprague-Dawley rats (2 males given 5 mg/kg bw in propylene glycol:glycerol by gavage), a beagle dog (1 female given 3.5 mg/kg bw in sesame oil by gavage) and cattle (5 males given 0.2 mg/kg bw subcutaneously). /The following metabolites were identified in/... the liver and feces from each species and the fat of cattle... /unchanged doramectin, 3"-O-desmethyl doramectin, 24-hydroxymethyl doramectin, and 24-hydroxymethyl-3"-O-desmethyl doramectin./

来源:Hazardous Substances Data Bank (HSDB)

代谢

多拉霉素的代谢产物在所有研究的物种（大鼠、狗、猪、牛）中相似。这些代谢物比多拉霉素更具极性，是由于远端糖环的脱甲基化、24-甲基羟基化以及这两种生物转化的结合产物。

The products of doramectin metabolism were similar in all species investigated /rats, dogs, pigs, cattle/. The metabolites were more polar than doramectin and were the result of O-demethylation in the distal saccharide ring, of hydroxylation of the 24-methyl group and a combination of both of these biotransformations.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道（如需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。密切观察呼吸不足的迹象，并在需要时辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，并在必要时进行治疗……。监测休克，并在必要时进行治疗……。预防癫痫，并在必要时进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的呕吐反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污染后，用干性无菌敷料覆盖皮肤烧伤……。/毒物A和B/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于昏迷的患者、严重肺水肿的患者或严重呼吸窘迫的患者，考虑进行口咽或鼻咽气管插管以控制气道。使用带气囊的面罩进行正压通气技术可能有益。考虑对肺水肿进行药物治疗...。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇...。监测心率和必要时治疗心律失常...。开始静脉输注D5W/SRP：“保持开放”，最小流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸钠林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象...。使用地西泮或劳拉西泮治疗癫痫...。使用丙美卡因氢氯化物协助眼部冲洗...。/毒物A和B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/多拉菌素以0.5克量在闭合贴片下应用于3只新西兰白兔的正常和磨损皮肤上，持续24小时。在剂量后24小时和48小时，1个完整部位和2个磨损部位观察到轻微红斑。在任何部位都没有水肿，且在剂量后72小时所有部位看起来都正常。

/LABORATORY ANIMALS: Acute Exposure/ Doramectin was applied to normal and abraded skin of 3 New Zealand white rabbits (0.5 g under an occlusive patch) for 24 hours. Slight erythema was observed 24 and 48 hours post-dose at 1 of 3 intact sites and 2 of 3 abraded sites. There was no edema at any site and all sites appeared normal 72 hours post-dose.

来源:Hazardous Substances Data Bank (HSDB)