Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: Search for signals
Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: Search for signals
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DOI：
10.1002/hep.22272
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发表时间：
2008-06-01
期刊：
影响因子：
13.5
通讯作者：
Chalasani, Naga
中科院分区：
文献类型：
--
作者：
Lammert, Craig;Einarsson, Stefan;Chalasani, Naga
特异性药物性肝损伤(DILI)传统上被认为与剂量无关。然而，有人指出，大多数因肝脏毒性而被撤回市场或收到黑盒警告的药物，每天的处方剂量都超过50毫克。为了检验每日服药剂量与特质DILI之间的关系，我们进行了一项有两个目的的研究。首先，使用两个药物数据库，我们检查了美国常用处方药的每日剂量与其选定的肝脏不良事件报告频率之间的关系。其次，我们研究了瑞典药物不良反应咨询委员会(1970-2004年)报告的严重DILI病例，以寻找任何支持每日剂量与特殊DILI之间关系的信号。药物分为+50毫克/天组。在美国处方药中，每日口服药物剂量与肝功能衰竭(P=0.009)、肝移植(P<；0.001)和DILI引起的死亡(P=0.004)之间有统计学意义的关系，但与丙氨酸氨基转移酶(ALT)和谷草转氨酶(ALT；3)正常上限(P=0.10)或黄疸(P=0.16)无关。在598例符合条件的瑞典DILI病例中，9%属于=50 mg/d。在瑞典DILI病例中，每日剂量与不良结局(死亡或肝移植)之间有统计学意义的关系(=50 mg/天组分别为2%、9.4%和13.2%，P=0.03)。结论：这些数据表明每日口服处方药的剂量与特殊的DILI有关。需要更多的研究来验证这些观察结果，并探索它们的影响。
Idiosyncratic drug-induced liver injury (DILI) is traditionally thought not to be dose-related. However, it has been pointed out that most medicines that were withdrawn from marketing or received a black-box warning because of hepatotoxicity were prescribed at daily doses greater than 50 mg/day. To examine the relationship between daily dose of medications and idiosyncratic DILI, we conducted a study with two aims. First, using two pharmaceutical databases, we examined the relationship between daily dose of commonly prescribed medicines in the United States and reported frequency of their selected hepatic adverse events. Second, we examined serious DILI cases reported to the Swedish Adverse Drug Reactions Advisory Committee (1970-2004) for any signals supporting the relationship between daily dose and idiosyncratic DILI. Medications were categorized into = 50 mg/day groups. Among US prescription medicines, a statistically significant relationship was observed between daily dose of oral medicines and reports of liver failure (P = 0.009), liver transplantation (P < 0.001), and death caused by DILI (P = 0.004) but not alanine aminotransferase (ALT) > 3 x upper limit of normal (P = 0.10) or jaundice (P = 0.16). Of 598 eligible Swedish DILI cases, 9% belonged to the = 50 mg/day. A statistically significant relationship was noted between daily dose and poor outcome (death or liver transplantation) of Swedish DILI cases (2%,9.4%, and 13.2% in = 50 mg/day groups, respectively, P = 0.03). Conclusion: These data suggest a relationship between daily doses of oral prescription medications and idiosyncratic DILI. More studies are needed to validate these observations and to explore their implications.