毒理性
青蒿素衍生物与血清转氨酶升高（1%至4%）的低发生率有关，这通常是无症状的、轻到中度且自限性的，即使在继续治疗的情况下也往往会解决。在大多数研究中，青蒿素治疗期间血清ALT升高的发生率与接受比较药物治疗的患者相似。然而，重要的是，越来越多的报告指出，服用青蒿素衍生物的患者出现了特异反应性急性肝损伤。然而，解释这些报告的复杂性在于，大多数严重肝损伤的病例发生在同时接受其他抗疟疾药物的患者中，其中一些已知具有肝毒性（如阿莫地喹、磺胺甲恶唑、磺胺嘧啶/乙胺嘧啶）。损伤通常在开始使用青蒿素后的几天到几周内发生，血清酶升高的模式通常是肝细胞型。超敏反应的特征，如皮疹、发热和嗜酸性粒细胞增多不常见，没有描述自体抗体。症状可能类似于急性病毒性肝炎，肝炎可能很严重，已经报道了几例需要紧急肝移植的致命情况或病例。尽管如此，由于青蒿素衍生物导致的临床上明显的肝损伤非常罕见，在几项大型疟疾治疗临床试验中并未报告。大多数已发表的关于青蒿素肝毒性的报告都与使用含有青蒿素的草药补充剂以及延长治疗有关。
Artemisinin derivatives have been associated with a low rate of serum aminotransferase elevations (1% to 4%) that are generally asymptomatic, mild-to-moderate and self-limited, often resolving even with continuing therapy. In most studies, the rate of serum ALT elevations during artemisinin therapy was similar to that of patients on comparator agents. Importantly, there have been increasing numbers of reports of idiosyncratic acute liver injury in patients taking artemisinin derivatives. Complicating the interpretation of these reports, however, is that most severe cases of liver injury occurred in patients who were also receiving other antimalarial agents, some of which are known to be hepatotoxic (amodiaquine, sulfamethoxazole, sulfadiazine/pyrimethamine). The onset of injury was usually within a few days to weeks of starting artemisinin, and the pattern of serum enzyme elevations was typically hepatocellular. Features of hypersensitivity such as rash, fever and eosinophilia were uncommon and autoantibodies have not been described. Symptoms can resemble those of acute viral hepatitis and the hepatitis can be severe, and several fatal instances or cases requiring emergency liver transplantation have been reported. Nevertheless, clinically apparent liver injury due to artemisinin derivatives is very rare and was not reported in several large clinical trials of malaria treatment. Most published reports of hepatotoxicity of artemisinin were linked to use of herbal supplements containing artemisinin and with extended treatment.
来源:LiverTox
