Azane;platinum(4+);dichloride

• 分子结构分类: 无机化合物 - 混合金属/非金属化合物 - 过渡金属盐
• 英文名称: Azane;platinum(4+);dichloride
• 英文别名: azane;platinum(4+);dichloride
• 化学式: Cl2H6N2Pt+2
• 分子量: 300.05
• InChiKey: BSJGASKRWFKGMV-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  5
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  2
• 氢给体数：
  2
• 氢受体数：
  2

ADMET

代谢

消除途径：母化合物顺铂通过尿液排出。尽管在给予顺铂后胆汁和大肠中存在少量铂，但铂的粪便排泄似乎是不重要的。 半衰期：顺铂在给药50或100 mg/m^2后以单指数形式衰减，半衰期为20至30分钟。顺铂的血浆半衰期为30分钟。顺铂中的铂与白蛋白形成的复合物不会显著解离，并且以最短五天或更长的半衰期缓慢消除。

Route of Elimination: The parent compound, cisplatin, is excreted in the urine. Although small amounts of platinum are present in the bile and large intestine after administration of cisplatin, the fecal excretion of platinum appears to be insignificant. Half Life: Cisplatin decays monoexponentially with a half life of 20 to 30 minutes following administrations of 50 or 100 mg/m^2. Cisplatin has a plasma half-life of 30 minutes. The complexes between albumin and the platinum from cisplatin do not dissociate to a significant extent and are slowly eliminated with a minimum half-life of five days or more.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

烷基化剂通过三种不同的机制发挥作用：1）将烷基团附着到DNA碱基上，导致DNA在修复酶试图替换烷基化碱基的过程中被切碎，从而阻止受影响的DNA的合成和RNA转录；2）通过形成交联（DNA中原子之间的键）对DNA造成损伤，防止DNA分离以进行合成或转录；3）诱导核苷酸的错配，导致突变。

Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 药物性肝损伤

化合物：顺铂

Compound:cisplatin

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注解：较少的药物性肝损伤关注

DILI Annotation:Less-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重性等级：3

Severity Grade:3

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：警告和预防措施

Label Section:Warnings and precautions

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

在给予20至120 mg/m^2顺铂剂量后，铂的浓度在肝脏、前列腺和肾脏中最高；在膀胱、肌肉、睾丸、胰腺和脾脏中略低；在肠道、肾上腺、心脏、肺、大脑和脑干中最低。最后一次给药后，铂在组织中可存在长达180天。

Following cisplatin doses of 20 to 120 mg/m^2, the concentrations of platinum are highest in liver, prostate, and kidney; somewhat lower in bladder, muscle, testicle, pancreas, and spleen; and lowest in bowel, adrenal, heart, lung, cerebrum, and cerebellum. Platinum is present in tissues for as long as 180 days after the last administration.

来源:DrugBank

吸收、分配和排泄

• 消除途径

顺铂是一种母化合物，通过尿液排出。尽管在给予顺铂后胆汁和大肠中存在少量铂，但铂的粪便排泄似乎并不显著。

The parent compound, cisplatin, is excreted in the urine. Although small amounts of platinum are present in the bile and large intestine after administration of cisplatin, the fecal excretion of platinum appears to be insignificant.

来源:DrugBank

吸收、分配和排泄

• 分布容积

稳态分布容积 = 11-12 L/m^2

Volume of distribution at steady state = 11-12 L/m^2

来源:DrugBank

吸收、分配和排泄

• 清除

15-16 L/h/m^2 [总清除率，100 mg/m^2 7小时输注] 62 mL/min/m^2 [肾清除率，100 mg/m^2 2小时输注] 50 mL/min/m^2 [肾清除率，100 mg/m^2 6至7小时输注] 游离（超滤过）铂的肾清除率也超过了肾小球滤过率，这表明顺铂或其他含铂分子是被肾脏积极分泌的。游离铂的肾清除率是非线性的，并且是可变的，取决于剂量、尿流率以及个体在积极分泌和可能的肾小管重吸收方面的变异性。

15-16 L/h/m^2 [total body clearance, 7-hour infusion of 100 mg/m^2] 62 mL/min/m^2 [renal clearance, 2-hour infusion of 100 mg/m^2] 50 mL/min/m^2 [renal clearance, 6- to 7-hour infusion of 100 mg/m^2] The renal clearance of free (ultrafilterable) platinum also exceeds the glomerular filtration rate indicating that cisplatin or other platinum-containing molecules are actively secreted by the kidneys. The renal clearance of free platinum is nonlinear and variable and is dependent on dose, urine flow rate, and individual variability in the extent of active secretion and possible tubular reabsorption.

来源:DrugBank