Folate disodium | 6484-89-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: Folate disodium
• 英文别名: disodium;(2S)-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioate
• CAS: 6484-89-5；29704-76-5
• 化学式: C19H17N7Na2O6
• 分子量: 485.4
• InChiKey: SWIRFWUEJODNRG-LTCKWSDVSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -8.71
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  215
• 氢给体数：
  4
• 氢受体数：
  9

ADMET

毒理性

• 肝毒性

培美曲塞治疗与血清酶水平低至中度升高有关，但这些通常较轻、短暂，且不伴有症状或黄疸。血清ALT或AST升高超过5倍ULN的患者占1%至6%，但通常病程自限，很少需要调整剂量或停药。没有报告因培美曲塞引起的临床明显的急性肝损伤病例。此外，培美曲塞并未与 sinusoidal obSTruction syndrome（肝窦阻塞综合征）或乙型肝炎的再激活有关联，但培美曲塞在高剂量用于肿瘤性疾病或骨髓移植的预处理方案中很少使用，这些情况下其他肿瘤药物常与这些并发症有关。

Pemetrexed therapy is associated with a low-to-moderate rate of serum enzyme elevations, but these are generally mild, transient and without accompanying symptoms or jaundice. Serum ALT or AST elevations above 5 times ULN occur in 1% to 6% of patients, but are usually self-limited in course and rarely require dose modification or discontinuation. No instances of clinically apparent acute liver injury attributed to pemetrexed have been reported. In addition, pemetrexed has not been linked to sinusoidal obstruction syndrome or to reactivation of hepatitis B, but it is rarely used in high doses in neoplastic disease or in conditioning regimens for bone marrow transplantation, situations in which other neoplastic agents are commonly associated with these complications.

来源:LiverTox

毒理性

• 肝毒性

Pralatrexate 在治疗期间与血清酶水平升高有关，但这些异常通常是轻微和自限性的，2%至6%的患者会升高至超过正常上限(ULN)的5倍以上，很少需要调整剂量。文献中没有报告因普拉拉雷克酸引起的临床明显的急性肝损伤的案例，但建议监测肝毒性。普拉拉雷克酸并没有特别与 sinusoidal obstruction syndrome (门脉高压症) 相关联，但它在恶性疾病中高剂量使用或在骨髓移植的预处理方案中很少使用，而这些情况下，烷化剂通常与这种并发症有关。

Pralatrexate is associated with serum enzyme elevations during therapy, but these abnormalities are generally mild and self-limited, rising to above 5 times ULN in 2% to 6% of patients and rarely requiring dose adjustment. No instances of clinically apparent acute liver injury attributed to pralatrexate have been reported in the literature, but monitoring for liver toxicity is recommended. Pralatrexate has not been linked specifically to sinusoidal obstruction syndrome, but it is rarely used in high doses in neoplastic disease or in conditioning regimens for bone marrow transplantation, situations in which alkylating agents are commonly associated with this complication.

来源:LiverTox

毒理性

• 肝毒性

当不给予亚叶酸钙保护时，三甲曲沙治疗与血清酶升高的中等发生率相关，高达20%的患者血清ALT或AST升高超过5倍ULN。然而，当与亚叶酸钙一起使用时，三甲曲沙的副作用较少，尽管仍可能发生血清酶升高。在HIV感染和耶氏肺孢子菌肺炎患者的临床试验中，ALT升高超过5倍ULN的发生率为1%至8%，但通常不比使用甲氧苄啶和磺胺甲恶唑的标准化疗更频繁。这些升高通常是暂时的，没有伴随症状或黄疸，尽管继续治疗，但已解决或改善。文献中没有报道三甲曲沙引起的临床明显急性肝损伤的实例。此外，三甲曲沙没有与窦状阻塞综合征或乙型肝炎的再激活相关。尽管如此，三甲曲沙可能具有肝毒性潜力，但由于其使用有限，使用时间短，并且与亚叶酸钙一起使用，因此没有令人信服地将其与出现黄疸的临床明显肝损伤病例联系起来。

When given without leucovorin protection, trimetrexate therapy is associated with a moderate rate of serum enzyme elevations, serum ALT or AST elevations above 5 times ULN in up to 20% of patients. When given with leucovorin, however, trimetrexate has fewer side effects although serum enzyme elevations can still occur. In clinical trials in patients with HIV infection and Pneumocystis jirovecii pneumonia, ALT elevations above 5 times ULN occurred in 1% to 8% of patients, but were usually no more frequent than with standard therapy using trimethoprim with sulfamethoxazole. The elevations were typically transient, without accompanying symptoms or jaundice and resolved or improved despite continuation of therapy. No instances of clinically apparent acute liver injury attributed to trimetrexate have been reported in the literature. In addition, trimetrexate has not been linked to sinusoidal obstruction syndrome or to reactivation of hepatitis B. Nevertheless, trimetrexate probably has hepatotoxic potential, but because it has limited use, is given for short periods of time and is administered with leucovorin, it has not been convincingly linked to cases of clinically apparent liver injury with jaundice.

来源:LiverTox