毒理性
紫杉醇与7%至26%的患者血清转氨酶升高有关，但在接受最高剂量的患者中，超过正常上限5倍的情况仅占2%。碱性磷酸酶升高的比例相似，偶尔也会出现轻度胆红素升高。这些异常通常是无需调整剂量或停药的无症状、轻度且自限性的。紫杉醇并未明确与迟发性、特异性的临床明显肝损伤和黄疸的实例有关联。然而，紫杉醇输注时发生的超敏反应可能很严重，并伴有急性肝坏死。肝脏损伤可能相对较轻且不伴有黄疸（案例1），但也可能很严重，迅速出现多器官衰竭和死亡。文献中至少有一例关于紫杉醇超敏反应后急性肝衰竭的报道，最近紫杉醇和多西他赛的产品标签修改提到了严重输注反应后发生的毒性死亡。由于紫杉醇通常与其他抗肿瘤药物联合使用，治疗期间发生的肝损伤不能总是可靠地归因于紫杉醇而不是其他特定药物。此外，紫杉醇与其他抗癌药物联合使用可能与乙型肝炎的复发、机会性病毒感染的风险增加、窦道阻塞综合征或败血症有关，这些都可能导致肝功能测试异常或临床明显的肝损伤。
Paclitaxel has been associated with serum aminotransferase elevations in 7% to 26% of patients, but values greater than 5 times the upper limit of normal (ULN) in only 2% of those receiving the highest doses. Similar rates of alkaline phosphatase elevations and occasional mild bilirubin elevations also occur. The abnormalities are usually asymptomatic, mild and self-limited, rarely requiring dose modification or discontinuation. Paclitaxel has not been linked convincingly to instances of delayed, idiosyncratic clinically apparent liver injury with jaundice. However, the hypersensitivity reactions that occur with infusions of paclitaxel can be severe and accompanied by acute hepatic necrosis. The liver injury may be relatively mild and anicteric (Case 1), but can also be severe with rapid onset of multiorgan failure and death. At least one instance of acute liver failure following a hypersensitivity reaction to paclitaxel has been published in the literature and recent modifications of the product labels for paclitaxel and docetaxel mention the occurrence of toxic deaths following severe infusion reactions. Because paclitaxel is often given with other antineoplastic agents, liver injury arising during therapy cannot always be reliably attributed to paclitaxel rather than to other specific agents. Furthermore, paclitaxel in combination with other anticancer agents may be associated with reactivation of hepatitis B, increased risk of opportunistic viral infections, sinusoidal obstruction syndrome or sepsis, any of which can cause liver test abnormalities or clinically apparent liver injury.
来源:LiverTox
