Phentermine/topiramate | 960078-81-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Phentermine/topiramate
• 英文别名: 2-methyl-1-phenylpropan-2-amine;[(1R,6S,9R)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.02,6]dodecan-6-yl]methyl sulfamate
• CAS: 960078-81-3
• 化学式: C22H36N2O8S
• 分子量: 488.6
• InChiKey: PWDLDBWXTVILPC-QGGVPXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.57
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  10

ADMET

毒理性

• 肝毒性

在上市前临床试验中，接受芬特明和托吡酯联合治疗的患者的血清转氨酶升高情况并不比接受安慰剂的患者更常见。临床上明显的由这种联合用药导致的肝损伤尚未有报道，但是已经有一些急性肝损伤的案例与单独使用托吡酯治疗其他病症有关。归因于托吡酯的肝损伤病例报告主要发生在接受其他已知具有肝毒性的抗惊厥药物的患者中。托吡酯通过细胞色素P450系统代谢，已知能诱导CYP 3A4活性并改变其他抗惊厥药物的浓度水平，从而增加肝损伤的风险。单独使用托吡酯并未与严重的肝损伤有关联。

In premarketing clinical trials, serum aminotransferase elevations were no more common among patients receiving the combination of phentermine and topiramate than placebo. Clinically apparent liver injury due to this combination has not been reported, but several instances of acute liver injury have been linked to topiramate monotherapy of other conditions. Case reports of liver injury attributed to topiramate have occurred largely in patients with seizure disorders who were receiving other anticonvulsants with known hepatotoxic potential. Topiramate is metabolized by the cytochrome P450 system and is known to induce CYP 3A4 activity and alter the levels of other anticonvulsants, thus predisposing to hepatic injury. By itself, topiramate has not been linked to severe hepatic injury.

来源:LiverTox