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药物性肝损伤(drug induced liver injury,DILI)对患者的健康具有重要影响,DILI会影响药物在临床的使用,甚至药物撤市。对乙酰氨基酚(acetaminophen,APAP)是临床常用药物,其肝毒性已有大量的报道[1-3],APAP常用剂量小于2g·d-1,若大于4 g·d-1,可致肝损害,大于10 g·d-1可致死亡。因此,美国食品药品管理局(FDA)要求生产厂家修改药品说明书,标明过量应用APAP可导致肝脏毒性反应。肝细胞色素P450在药物代谢中起着重要的作用。细胞色素酶P450广泛分布于哺乳动物的组织器官中,其中,肝脏和肠管含量最高[4]。约有20种细胞色素酶P450参与药物的代谢,如果代谢某种药物的酶缺乏或受抑制时,可表现为该药物的血药浓度升高,半衰期延长,导致毒性反应增加[5]。
Drug-induced liver injury (DILI) has a significant impact on the patient’s health. DILI affects the clinical use of drugs and even the withdrawal of drugs. Acetaminophen (APAP) is a commonly used clinical drug, and its hepatotoxicity has been widely reported [1-3], APAP commonly used dose less than 2g · d-1, if greater than 4g · d-1, can cause liver Damage, greater than 10 g · d-1 can cause death. Therefore, the US Food and Drug Administration (FDA) requires manufacturers to amend the drug specification, indicating that the excessive use of APAP can lead to liver toxicity. Cytochrome P450 plays an important role in drug metabolism. Cytochrome P450 is widely distributed in mammalian tissues and organs, with the highest content of liver and intestine [4]. About 20 kinds of cytochrome P450 involved in drug metabolism, if the metabolism of a drug enzyme deficiency or suppressed, the performance of the drug for the blood concentration, prolonged half-life, leading to increased toxicity [5].