(1R,9S,10S)-17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene-4,10-diol | 58786-99-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (1R,9S,10S)-17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene-4,10-diol
• CAS: 58786-99-5
• 化学式: C₂₁H₂₉NO₂
• 分子量: 327.5
• InChiKey: IFKLAQQSCNILHL-PWRODBHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

广泛在肝脏代谢。丁氧芬代谢物在人体内的药理活性尚未进行研究；在动物研究中，丁氧芬代谢物显示出一定的镇痛活性。

Extensively metabolized in the liver. The pharmacological activity of butorphanol metabolites has not been studied in humans; in animal studies, butorphanol metabolites have demonstrated some analgesic activity.

来源:DrugBank

代谢

布托啡诺在肝脏广泛代谢。布托啡诺代谢物在人体内的药理活性尚未研究；在动物研究中，布托啡诺代谢物显示出一定的镇痛活性。 消除途径：布托啡诺在肝脏广泛代谢。通过尿液和粪便排出体外。 半衰期：布托啡诺的消除半衰期约为18小时。在肾功能受损的患者（肌酐清除率<30 mL/min）中，消除半衰期大约加倍。在静脉给药给肝功能受损的患者后，布托啡诺的消除半衰期大约增加三倍。

Extensively metabolized in the liver. The pharmacological activity of butorphanol metabolites has not been studied in humans; in animal studies, butorphanol metabolites have demonstrated some analgesic activity. Route of Elimination: Butorphanol is extensively metabolized in the liver. Elimination occurs by urine and fecal excretion. Half Life: The elimination half-life of butorphanol is about 18 hours. In renally impaired patients with creatinine clearances &lt;30 mL/min the elimination half-life is approximately doubled. After intravenous administration to patients with hepatic impairment, the elimination half-life of butorphanol was approximately tripled.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

作用机制尚不清楚，但认为其与中枢神经系统中的阿片受体位点（可能位于或与边缘系统相关）相互作用。阿片拮抗作用可能是由于在阿片受体上的竞争性抑制，但也可能是其他机制的结果。布托啡诺是一种混合激动-拮抗剂，在阿片μ受体位点上发挥拮抗或部分拮抗作用，但认为

The exact mechanism of action is unknown, but is believed to interact with an opiate receptor site in the CNS (probably in or associated with the limbic system). The opiate antagonistic effect may result from competitive inhibition at the opiate receptor, but may also be a result of other mechanisms. Butorphanol is a mixed agonist-antagonist that exerts antagonistic or partially antagonistic effects at mu opiate receptor sites, but is thought to exert its agonistic effects principally at the kappa and sigma opiate receptors. Its interactions with these receptors in the central nervous system apparently mediate most of its pharmacologic effects, including analgesia.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

医学问题可能包括肺充血、肝病、破伤风、心脏瓣膜感染、皮肤脓肿、贫血和肺炎。过量使用可能导致死亡。

Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

肌肉注射后迅速吸收，20-40分钟内达到血浆峰值。绝对生物利用度为60-70%，在有过敏鼻炎的患者中保持不变。在使用鼻血管收缩剂（羟甲唑啉）的患者中，吸收的剂量比例未改变，但吸收速率减慢。口服生物利用度仅为5-17%，这是因为首次通过肝脏代谢广泛。

Rapidly absorbed after intramuscular injection and peak plasma levels are reached in 20-40 minutes. The absolute bioavailability is 60-70% and is unchanged in patients with allergic rhinitis. In patients using a nasal vasoconstrictor (oxymetazoline) the fraction of the dose absorbed was unchanged, but the rate of absorption was slowed. Oral bioavailability is only 5-17% because of extensive first-pass metabolism.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

丁丙诺啡过量的临床表现通常是阿片类药物的一般症状。最严重的症状是呼吸不足、心血管功能不足、昏迷和死亡。医疗问题可能包括肺充血、肝病、破伤风、心脏瓣膜感染、皮肤脓肿、贫血和肺炎。过量可能会导致死亡。

The clinical manifestations of butorphanol overdose are those of opioid drugs in general. The most serious symptoms are hypoventilation, cardiovascular insufficiency, coma, and death. Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

肌肉注射后迅速吸收，20-40分钟内达到血浆峰值。绝对生物利用度为60-70%，在有过敏鼻炎的患者中这一点保持不变。在使用鼻血管收缩剂（羟甲唑啉）的患者中，吸收的剂量比例保持不变，但吸收速率减慢。口服生物利用度仅为5-17%，这是因为首次通过肝脏代谢广泛。

Rapidly absorbed after intramuscular injection and peak plasma levels are reached in 20-40 minutes. The absolute bioavailability is 60-70% and is unchanged in patients with allergic rhinitis. In patients using a nasal vasoconstrictor (oxymetazoline) the fraction of the dose absorbed was unchanged, but the rate of absorption was slowed. Oral bioavailability is only 5-17% because of extensive first-pass metabolism.

来源:DrugBank

吸收、分配和排泄

• 消除途径

布托啡诺在肝脏中被广泛代谢。消除通过尿液和粪便排泄。

Butorphanol is extensively metabolized in the liver. Elimination occurs by urine and fecal excretion.

来源:DrugBank

吸收、分配和排泄

• 分布容积

从305到901 L

305 to 901 L

来源:DrugBank

吸收、分配和排泄

• 清除

99 ± 23 升/小时 [静脉注射 2 毫克 青年]

99 +/- 23 L/h [Young with IV 2 mg]

来源:DrugBank