goserelin | 65807-02-5

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 促性激素类药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: goserelin
• 英文别名: gosorelin；zoladex；Glp-His-Trp-Ser-Tyr-Ser(tBu)-Leu-Arg-Pro-azaGly-NH₂；[D-Ser (But)⁶, Azgly¹⁰] GnRH；(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide
• CAS: 65807-02-5
• 化学式: C₅₉H₈₄N₁₈O₁₄
• 分子量: 1269.43
• InChiKey: BLCLNMBMMGCOAS-URPVMXJPSA-N

物化性质

• 密度：
  1.50±0.1 g/cm3(Predicted)
• 溶解度：
  H2O：20 mg/mL，澄清，无色
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  91
• 可旋转键数：
  32
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  496
• 氢给体数：
  17
• 氢受体数：
  16

ADMET

代谢

肝脏的

Hepatic

来源:DrugBank

代谢

戈舍瑞林通过C端氨基酸的水解进行代谢，这是其主要清除机制。血清中主要循环成分似乎是1-7片段，而在一名健康男性志愿者的尿液中主要存在的成分是5-10片段。人类中戈舍瑞林的代谢产生了一组类似的但范围较窄的代谢物，这些代谢物在其他物种中也有发现。在人类中发现的所有代谢物在毒理学物种中也都有发现。

Metabolism of goserelin, by hydrolysis of the C-terminal amino acids, is the major clearance mechanism. The major circulating component in serum appeared to be 1-7 fragment, and the major component present in urine of one healthy male volunteer was 5-10 fragment. The metabolism of goserelin in humans yields a similar but narrow profile of metabolites to that found in other species. All metabolites found in humans have also been found in toxicology species.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 肝毒性

戈舍瑞林治疗期间，有3%至5%的患者会出现轻度的血清酶水平升高，但高于正常上限3倍的情况非常罕见，报告的发生率不到1%。戈舍瑞林治疗期间血清酶的升高通常是暂时的和无症状的，即使在继续用药的情况下也会自行解决，很少需要调整剂量或停药。尽管戈舍瑞林已经使用了几十年，但仅与一例临床明显的肝损伤有关，而且这一案例并不完全令人信服。因此，不建议常规监测患者的肝功能测试异常。

Goserelin has been associated with mild serum enzyme elevations during therapy in 3% to 5% of patients, but values above 3 times the upper limit of normal are rare, being reported in less than 1% of recipients. The serum enzyme elevations during goserelin therapy have generally been transient and asymptomatic, resolving even with drug continuation and rarely requiring dose modification or discontinuation. Despite use for several decades, goserelin has been linked to only a single, and not entirely convincing, case of clinically apparent liver injury. Routine monitoring of patients for liver test abnormalities is not recommended.

来源:LiverTox

毒理性

• 药物性肝损伤

戈舍瑞林

Compound:goserelin

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI标注：模糊的DILI关注

DILI Annotation:Ambiguous DILI-concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重程度等级：3

Severity Grade:3

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

不良反应部分

Label Section:Adverse reactions

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

口服不活跃，皮下给药后迅速吸收。

Inactive orally, rapidly absorbed following subcutaneous administration.

来源:DrugBank

吸收、分配和排泄

• 消除途径

在皮下注射戈舍瑞林放射性溶液后，戈舍瑞林的清除非常迅速，通过肝脏和尿液排泄的组合发生。超过90%的戈舍瑞林放射性溶液配方剂量通过尿液排出。

Clearance of goserelin following subcutaneous administration of a radiolabeled solution of goserelin was very rapid and occurred via a combination of hepatic and urinary excretion. More than 90% of a subcutaneous radiolabeled solution formulation dose of goserelin was excreted in urine.

来源:DrugBank

吸收、分配和排泄

• 分布容积

44.1 ± 13.6 升 [皮下注射250微克]

44.1 ± 13.6 L [subcutaneous administration of 250 mcg]

来源:DrugBank

吸收、分配和排泄

• 清除

前列腺癌，每分钟血液流量为121毫升加减42.4毫升 [使用10.8毫克药物]

121 +/- 42.4 mL/min [prostate cancer with 10.8 mg depot]

来源:DrugBank

吸收、分配和排泄

250微克戈舍瑞林水溶液皮下给药后，健康男性的表观分布容积为44.1 + 或 - 13.6升。戈舍瑞林的血浆蛋白结合率发现为27%。

The apparent volume of distribution determined after subcutaneous administration of 250 ug aqueous solution of goserelin was 44.1 + or - 13.6 liters for healthy males. The plasma protein binding of goserelin was found to be 27%.

来源:Hazardous Substances Data Bank (HSDB)