[(4R,4aS,7aR,12bS)-9-methoxy-3-methyl-2,4,4a,5,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl] benzoate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: [(4R,4aS,7aR,12bS)-9-methoxy-3-methyl-2,4,4a,5,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl] benzoate
• 化学式: C₂₅H₂₅NO₄
• 分子量: 403.5
• InChiKey: VPMRSLWWUXNYRY-NDOYXKHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

ADMET

代谢

Benzhydrocodone 通过肠道酶迅速代谢成氢可酮。氢可酮通过 CYP3A4 和 CYP2D6 进行氧化代谢，分别有助于 N-去甲基化和 O-去甲基化。去烷基代谢物进一步进行 6-酮还原，形成 6-α-和 6-β-羟基代谢物，以及葡萄糖醛酸苷结合。

Benzhydrocodone is rapidly metabolized to hydrocodone by intestinal enzymes. Hydrocodone undergoes oxidative metabolism by CYP3A4 and CYP2D6 which contribute to N-demethylation and O-demethylation respectively. The dealkylated metabolites undergo further 6-ketoreduction to the 6-α- and 6-β-hydroxy metabolites as well as glucuronide conjugation.

来源:DrugBank

毒理性

• 毒性总结

盐酸羟考酮过量表现为阿片类药物中毒，包括呼吸抑制、嗜睡、昏迷、骨骼肌松弛、皮肤湿冷、瞳孔缩小、肺水肿、心动过缓、低血压、部分或完全气道阻塞、异常打鼾和死亡。过量时，首要任务是保持通畅和受保护的气道，必要时提供辅助通气。支持性措施，如静脉输液、补充氧气和血管加压药，可能用于管理循环休克。在心脏骤停或心律失常的情况下，可能需要高级生命支持。阿片类药物拮抗剂如纳洛酮可能用于逆转氢考酮的呼吸和循环效应。纳洛酮给药后仍需紧急监测，因为阿片类药物的效果可能会再次出现。此外，如果用于阿片类药物耐受的患者，纳洛酮可能会产生阿片类药物撤退症状。

Overdosage with benzhydrocodone presents as opioid intoxication including respiratory depression, somnolence, coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. In case of oversdosage the foremost priority is the maintenance of a patent and protected airway with the provision of assisted ventilation if necessary. Supportive measures such as IV fluids, supplemental oxygen, and vasopressors may be used to manage circulatory shock. Advanced life support may be necessary in the case of cardiac arrest or arrhythmias. Opioid antagonists such as [naloxone] may be used to reverse the respiratory and circulatory effects of hydrocodone. Emergency monitoring is still required after naloxone administration as the opioid effects may reappear. Additionally, if used in an opioid tolerant patient, naloxone may produce opioid withdrawal symptoms.

来源:DrugBank

吸收、分配和排泄

• 吸收

苯羟可酮的吸收曲线符合美国食品药品监督管理局（FDA）对类似即释氢可酮产品的生物等效性要求。苯羟可酮本身被肠道酶迅速代谢为活性代谢物氢可酮，而没有任何可检测的苯羟可酮进入血液循环。单次口服6.67毫克苯羟可酮可产生19.18纳克/毫升的Cmax，达峰时间（Tmax）为1.25小时，药时曲线下面积（AUC）为125.73小时*纳克/毫升。与食物同服可能会稍微延迟吸收，但对AUC没有显著影响。

The absorption profile of benzhydrocodone meets the FDA bioequivalence requirements for similar hydrocodone immediate-release products. Benzhydrocodone itself is rapidly metabolized by intestinal enzymes to the active metabolite, hydrocodone, with no detectable benzhydrocodone reaching circulation. Single oral doses of 6.67 mg benzhydrocodone produces a Cmax of 19.18 ng/mL with a Tmax of 1.25 h and an AUC of 125.73 h*ng/mL. Administration with food may slightly delay absorption but has no significant effect on AUC.

来源:DrugBank

吸收、分配和排泄

• 消除途径

氢可酮代谢物通过代谢和肾脏排泄的混合方式被消除。

The hydrocodone metabolite is eliminated through a mix of metabolism and renal excretion.

来源:DrugBank

吸收、分配和排泄

• 分布容积

苯氢可酮的氢吗啡酮代谢物具有714升的表观分布容积。

The hydrocodone metabolite of benzhydrocodone has an apparent volume of distribution of 714 L.

来源:DrugBank

吸收、分配和排泄

• 清除

氢可酮代谢物的表观清除率为64.4升/小时。

The apparent clearance of the hydrocodone metabolite is 64.4 L/h.

来源:DrugBank