SULINDAC-ASSOCIATED HEPATIC-INJURY - ANALYSIS OF 91 CASES REPORTED TO THE FOOD AND DRUG ADMINISTRATION
SULINDAC-ASSOCIATED HEPATIC-INJURY - ANALYSIS OF 91 CASES REPORTED TO THE FOOD AND DRUG ADMINISTRATION
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DOI：
10.1016/0016-5085(93)90428-f
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发表时间：
1993-02-01
期刊：
影响因子：
29.4
通讯作者：
EATON, RA
中科院分区：
文献类型：
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作者：
TARAZI, EM;HARTER, JG;EATON, RA
背景：最近对非类固醇抗炎药(NSAID)相关性肝损伤的重视模糊了非类固醇抗炎药之间的差异。因此，对个别非类固醇抗炎药引起的肝损伤进行检查似乎是有必要的。方法：在提交给美国食品和药物管理局的338篇报告中，247篇被认为舒林酸毒性不充分或不具说服力。对其余91例药物不良反应进行了分析。结果：共有4例死亡，其中3例死于严重过敏反应，1例死于暴发性肝衰竭。三分之二的病例有过敏的临床特征。男女之比为3.5：1，年龄在50岁以上者占69%。67%的患者出现黄疸。胆汁淤积型占43%，肝细胞型占25%，混合型占12%，不确定型占20%。胆汁淤积性损伤患者的嗜酸性粒细胞增多(40%)明显高于肝细胞损伤患者(0)。结论：舒林酸损伤女性多于男性。它可以导致胆汁淤积或肝细胞损伤，最常见的原因是免疫学特性。在一些患者中，代谢特性可能是其发病机制。这项研究说明了不良反应报告分析在确定药物引起的损伤中的作用。
Background:Recent emphasis on nonsteroidal anti-inflammatory drug (NSAID)-associated hepatic injury blurs differences between NSAIDs. Accordingly, examination of hepatic injury by individual NSAIDs seemed warranted. Sulindac-associated hepatic injury was selected.Methods:From 338 reports submitted to the Food and Drug Administration, 247 were considered inadequate or unconvincing for sulindac toxicity. The remaining 91 cases of reactions to the drug were analyzed. In 15 there was histological material available.Results:There were four deaths, three attributed to severe hypersensitivity and one to fulminant hepatic failure. Two thirds of the cases had clinical hallmarks of hypersensitivity. The ratio of females to males was 3.5:1; 69% of the patients were over 50 years of age. Jaundice was recorded in 67% of the patients. The pattern was cholestatic in 43%, hepatocellular in 25%, mixed in 12%, and indeterminate in 20% of the patients. Eosinophilia was significantly more frequent in patients with cholestatic injury (40%) than in those with hepatocellular injury (0).Conclusion:Sulindac injury involves females more than males. It can lead to cholestatic or hepatocellular injury, most often because of immunological idiosyncrasy. In some patients, metabolic idiosyncrasy may be the mechanism. This study illustrates the utility of analysis of adverse reaction reports in characterizing drug-induced injury.