Azane;cyclobutane-1,1-dicarboxylic acid;platinum(2+)

• 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: Azane;cyclobutane-1,1-dicarboxylic acid;platinum(2+)
• 化学式: C6H14N2O4Pt+2
• 分子量: 373.27
• InChiKey: OLESAACUTLOWQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.65
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  76.6
• 氢给体数：
  4
• 氢受体数：
  6

ADMET

代谢

卡铂主要以未改变的母化合物形式被消除。

Carboplatin is predominantly eliminated as the unchanged parent compound.

来源:DrugBank

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间的用途总结：大多数来源认为，接受抗癌治疗的母亲不应该哺乳，特别是使用卡铂等烷化剂。在间歇性治疗期间，如果有一个适当的禁乳期，可能可以安全地哺乳，但禁乳期的持续时间尚不清楚。随着化疗疗程的重复进行，乳汁中的铂含量可能会增加，而且还不清楚排入母乳中的铂的确切形式和毒性。哺乳婴儿会口服铂化合物，而不是静脉注射，婴儿对铂化合物的口服吸收情况尚不清楚。看起来，卡铂化疗后哺乳可能不安全，应停止哺乳。 化疗可能会不利地影响母乳的正常微生物组和化学成分。在怀孕期间接受化疗的妇女更可能有困难哺乳她们的婴儿。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：对74名在怀孕第二或第三季度在一家中心接受癌症化疗的妇女进行了电话随访研究，以确定她们产后是否成功哺乳。只有34%的妇女能够完全用母乳喂养她们的婴儿，66%的妇女报告遇到哺乳困难。与此相比，22位在怀孕期间被诊断出患有癌症但未接受化疗的母亲中，有91%的母亲成功哺乳。其他具有统计学意义的相关性包括：1. 有哺乳困难的母亲平均接受了5.5个周期的化疗，而没有困难的母亲平均接受了3.8个周期；2. 有哺乳困难的母亲在怀孕期间平均提前3.4周接受了第一次化疗周期。在接受含有类似药物顺铂方案的3名妇女中，有1人遇到了哺乳困难。

◉ Summary of Use during Lactation:Most sources consider that mothers receiving antineoplastic therapy should not breastfeed, especially with alkylating agents such as carboplatin. It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence, but the duration of abstinence is not clear. Platinum in milk may increase with repeated courses of chemotherapy and the exact form(s), and toxicity of platinum excreted into breastmilk are also not known. The nursing infant would receive platinum compounds orally rather than intravenously and oral absorption of platinum compounds by infants is not known. It appears that it is not safe to breastfeed after carboplatin chemotherapy, and breastfeeding should probably be discontinued. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 3 women who received a regimen containing the similar drug, cisplatin, 1 had breastfeeding difficulties.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 蛋白质结合

卡铂不与血浆蛋白结合。然而，游离的铂有40%不可逆地与血浆蛋白结合。

Carboplatin is not bound to plasma protein. However, the free platinum is 40% irreversibly bound to plasma proteins.

来源:DrugBank

吸收、分配和排泄

• 吸收

顺铂的Cmax和AUC随剂量的增加而成比例增加。75 mg/m2剂量的Cmax达到9.06 ± 0.74 µg/mL，AUC为27.18 ± 11.28 h*µg/mL。450 mg/m2剂量的Cmax达到55.39 ± 18.30 µg/mL，AUC为224.41 ± 69.07 h*µg/mL。

The Cmax and AUC of carboplatin increase proportionally with increasing doses. A 75 mg/m2 dose reaches a Cmax of 9.06 ± 0.74 µg/mL, with an AUC of 27.18 ± 11.28 h\*µg/mL. A 450 mg/m2 dose reaches a Cmax of 55.39 ± 18.30 µg/mL, with an AUC of 224.41 ± 69.07 h\*µg/mL.

来源:DrugBank

吸收、分配和排泄

• 消除途径

卡铂在12小时内通过尿液排出65%，在24小时内排出71%。从24小时到96小时，额外有3-5%通过尿液排出。胆汁排泄尚未确定。卡铂主要以未改变的母化合物形式排出。

Carboplatin is 65% eliminated in the urine within 12 hours, and 71% eliminated within 24 hours. An additional 3-5% is eliminated in urine from 24 hours to 96 hours. Biliary elimination has not been determined. Carboplatin is predominantly eliminated as the unchanged parent compound.

来源:DrugBank

吸收、分配和排泄

• 分布容积

30分钟静脉输注300-500 mg/m²后，表观分布容积为16升。

The apparent volume of distribution after a 30 minute intravenous infusion of 300-500 mg/m² was 16 L.

来源:DrugBank

吸收、分配和排泄

• 清除

30分钟静脉输注300-500 mg/m²后的总体清除率为4.4 L/h。

The total body clearance after a 30 minute intravenous infusion of 300-500 mg/m² was 4.4 L/h.

来源:DrugBank