钆膦维司三钠 | 193901-90-5

• 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
• 中文名称: 钆膦维司三钠
• 中文别名: 钆磷维塞三钠
• 英文名称: Trisodium;2-[[2-[bis(carboxylatomethyl)amino]-3-[(4,4-diphenylcyclohexyl)oxy-oxidophosphoryl]oxypropyl]-[2-[bis(carboxylatomethyl)amino]ethyl]amino]acetate;gadolinium(3+)
• 英文别名: trisodium;2-[[2-[bis(carboxylatomethyl)amino]-3-[(4,4-diphenylcyclohexyl)oxy-oxidophosphoryl]oxypropyl]-[2-[bis(carboxylatomethyl)amino]ethyl]amino]acetate;gadolinium(3+)
• CAS: 193901-90-5
• 化学式: C33H38GdN3Na3O14P
• 分子量: 957.9
• InChiKey: XGOSYNSWSRUASG-UHFFFAOYSA-H

物化性质

• 密度：
  1.1224 g/mL at 25 °C
• 粘度：
  3.0 cP at 20 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -14.55
• 重原子数：
  55
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  269
• 氢给体数：
  0
• 氢受体数：
  17

ADMET

代谢

Gadofosveset不经历可测量的代谢。

Gadofosveset does not undergo measurable metabolism.

来源:DrugBank

代谢

Gadofosveset在人体内不发生可测量的代谢。

Gadofosveset does not undergo measurable metabolism in humans.

来源:Hazardous Substances Data Bank (HSDB)

代谢

Gadofosveset在人体内不发生可测量的代谢。

Gadofosveset does not undergo measurable metabolism in humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

基于钆的对比剂会增加急性或慢性严重肾衰竭（肾小球滤过率小于30 mL/min/1.73m²）患者患肾源性系统性纤维化的风险。

Gadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with acute or chronic severe renal insufficiency (glomerular filtration rate < 30 mL/min/1.73m²).

来源:DrugBank

毒理性

• 毒性总结

识别：Gadofosveset用于磁共振血管成像（MRA）中作为对比剂，用于评估成人已知或疑似周围血管疾病的腹主动脉髂动脉闭塞性疾病（AIOD）。人类暴露和毒性：在临床试验中，Ablavar给药后45分钟观察到平均QTc从基线变化的轻微增加（2.8毫秒）；在24小时和72小时没有观察到增加。在Ablavar给药后45分钟，39/702（6%）的患者观察到QTc从基线变化30至60毫秒。在这个时间点，3/702（0.4%）的患者经历了QTc增加超过60毫秒。这些QTc延长并未与心律失常或症状相关。对于因QTc延长而心律失常高风险的患者（例如，合并用药，潜在的心脏状况），考虑获取基线心电图以帮助评估Ablavar给药的风险。如果给这些患者注射Ablavar，考虑进行随访心电图和风险降低措施（例如，患者咨询或密集的心电图监测），直到大部分Ablavar从血液中消除。在肾功能正常的患者中，大部分Ablavar在注射后72小时内从血液中消除。Ablavar可能会导致过敏性反应和/或过敏性休克，包括危及生命或致命的反应。在临床试验中，1676名受试者中有2名出现了过敏性反应和/或过敏性休克。在802名接受0.03 mmol/kg Ablavar治疗的患者中，常见的不良反应包括瘙痒、头痛、恶心、血管扩张、感觉异常、注射部位瘀伤、味觉异常、灼热感、静脉穿刺部位瘀伤、高血压、眩晕（不包括vertigo）、感觉寒冷。 动物研究：发育或生殖毒性/在生殖研究中，怀孕的大鼠和小鼠接受了不同剂量的Gadofosveset三钠，剂量高达人类剂量的约11倍（大鼠）和21.5倍（小鼠）（基于体表面积）。最高剂量在两个物种中均导致了母体毒性。在接受Gadofosveset三钠的小鼠中，剂量为人类剂量的3倍（基于体表面积），观察到植入后损失、吸收和死胎增加。在大鼠或小鼠后代中没有观察到胎儿异常。因为怀孕的动物接受了ABLAVAR的重复每日剂量，它们的总体暴露量显著高于单次给予人类的剂量。

IDENTIFICATION: Gadofosveset is indicated for use as a contrast agent in magnetic resonance angiography (MRA) to evaluate aortoiliac occlusive disease (AIOD) in adults with known or suspected peripheral vascular disease. HUMAN EXPOSURE AND TOXICITY: In clinical trials, a small increase (2.8 msec) in the average change from baseline in QTc was observed at 45 minutes following Ablavar administration; no increase was observed at 24 and 72 hours. A QTc change of 30 to 60 msec from baseline was observed in 39/702 (6%) patients at 45 min following Ablavar administration. At this time point, 3/702 (0.4%) patients experienced a QTc increase of > 60 msec. These QTc prolongations were not associated with arrhythmias or symptoms. In patients at high risk for arrhythmias due to QTc prolongation (e.g., concomitant medications, underlying cardiac conditions) consider obtaining baseline electrocardiograms to help assess the risks for Ablavar administration. If Ablavar is administered to these patients, consider follow-up electrocardiograms and risk reduction measures (e.g., patient counseling or intensive electrocardiography monitoring) until most Ablavar has been eliminated from the blood. In patients with normal renal function, most Ablavar was eliminated from the blood by 72 hours following injection. Ablavar may cause anaphylactoid and/or anaphylactic reactions, including life-threatening or fatal reactions. In clinical trials, anaphylactoid and/or anaphylactic reactions occurred in two of 1676 subjects. Common adverse reactions in 802 subjects receiving Ablavar at 0.03 mmol/kg are pruritis headache, nausea, vasodilatation, paresthesia injection site bruising, dysgeusia, burning sensation, venipuncture site bruise, hypertension, dizziness (excluding vertigo), feeling cold. ANIMAL STUDIES: Developmental or Reproductive Toxicity/ In reproductive studies, pregnant rats and rabbits received gadofosveset trisodium at various doses up to approximately 11 (rats) and 21.5 (rabbits) times the human dose (based on body surface area). The highest dose resulted in maternal toxicity in both species. In rabbits that received gadofosveset trisodium at 3 times the human dose (based on body surface area), increased post-implantation loss, resorptions, and dead fetuses were observed. Fetal anomalies were not observed in the rat or rabbit offspring. Because pregnant animals received repeated daily doses of ABLAVAR, their overall exposure was significantly higher than that achieved with a single dose administered to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 药物性肝损伤

化合物的名称:gadofosveset trisodium

Compound:gadofosveset trisodium

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注释：无 DILI（药物性肝损伤）担忧

DILI Annotation:No-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：无匹配

Label Section:No match

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 消除途径

Gadofosveset主要通过尿液排出，大约83.5%的注射剂量在14天内通过尿液排出。在最初的72小时内，有94%的尿液排泄发生。Gadofosveset的一小部分剂量会在粪便中回收（大约4.7%）。

Gadofosveset is eliminated primarily in the urine with approximately 83.5% of an injected dose excreted in the urine over 14 days. Ninety-four percent (94%) of urinary excretion occurs in the first 72 hours. A small portion of gadofosveset dose is recovered in feces (approximately 4.7%).

来源:DrugBank

吸收、分配和排泄

• 分布容积

48 ± 16 毫升/千克

48 ± 16 mL/kg

来源:DrugBank

吸收、分配和排泄

• 清除

在给予0.03毫摩尔/公斤后，以6.57 ± 0.97毫升/小时/公斤的速度。

6.57 ± 0.97 mL/h/kg following the administration of 0.03 mmol/kg.

来源:DrugBank

吸收、分配和排泄

Gadofosveset主要通过尿液排出，注射剂量的79%至94%（平均83.7%）在尿液中回收。在尿液中回收的Gadofosveset总量中，有94%在最初的72小时内回收。Gadofosveset剂量的一个小部分通过粪便回收（大约4.7%）。

Gadofosveset is eliminated primarily in the urine, with between 79% and 94% (mean of 83.7%) of an injected dose recovered in the urine. Of the total gadofosveset recovered in urine, 94% is recovered within the first 72 hours. A small portion of gadofosveset dose is recovered in feces (approximately 4.7%).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

稳态下钆酸fosveset的平均分布体积为148 +/- 16 mL/kg，大约相当于细胞外液的体积。循环中的钆酸fosveset有相当一部分与血浆蛋白结合，主要是白蛋白。在注射0.03 mmol/kg后的0.05、0.5、1和4小时内，钆酸fosveset的血浆蛋白结合率在79.8%到87.4%之间。

The mean volume of distribution at steady state for gadofosveset was 148 +/- 16 mL/kg, roughly equivalent to that of extracellular fluid. A significant portion of circulating gadofosveset is bound to plasma proteins, predominantly albumin. At 0.05, 0.5, 1 and 4 hours after injection of 0.03 mmol/kg the plasma protein binding of gadofosveset ranges from 79.8 to 87.4%.

来源:Hazardous Substances Data Bank (HSDB)