Etwel Fatma A, Rieder Michael J, Bend John R, Koren Gideon
Department of Medicine, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.
Drug Saf. 2008;31(2):169-80. doi: 10.2165/00002018-200831020-00006.
Pemoline is a CNS stimulant that was introduced in 1975 in the US and was used to treat children with attention deficit hyperactivity disorder. Pemoline was withdrawn from the market 30 years later because of fatal hepatotoxicity associated with its use.
To create a system that will estimate the potential association between a serious adverse event and a medication early in its marketing cycle.
All case reports of acute liver failure associated with pemoline and reported to the US FDA from 1975 through 1999 were reviewed. All published articles on pemoline-induced hepatotoxicity were reviewed, and the Naranjo adverse drug reaction probability scale was applied. The incidence rate of idiopathic acute liver failure was estimated from the published literature. The data were analyzed using Fisher's Exact test and relative risks (RR) were calculated.
As early as 1978, there was a significant signal indicating that pemoline was associated with acute liver failure, with an RR of 24.08 (95% CI 4.67, 124.10; p < 0.05). With an increased number of cases, the significance of the association had been steadily increased.
This method enables researchers, clinicians, drug companies and regulators to identify uncommon adverse drug reactions, caused mostly by new medications, earlier than they currently are in the course of marketing and thus quantify serious adverse events.
匹莫林是一种中枢神经系统兴奋剂，1975年在美国上市，用于治疗患有注意力缺陷多动障碍的儿童。30年后，由于其使用相关的致命肝毒性，匹莫林被撤出市场。
创建一个系统，以便在药物上市早期估计严重不良事件与药物之间的潜在关联。
回顾了1975年至1999年期间向美国食品药品监督管理局报告的所有与匹莫林相关的急性肝衰竭病例报告。查阅了所有关于匹莫林诱导肝毒性的已发表文章，并应用了纳伦霍药物不良反应概率量表。从已发表的文献中估计特发性急性肝衰竭的发病率。使用费舍尔精确检验分析数据并计算相对风险（RR）。
早在1978年，就有一个显著信号表明匹莫林与急性肝衰竭有关，RR为24.08（95%可信区间4.67，124.10；p<0.05）。随着病例数的增加，这种关联的显著性不断增加。
这种方法使研究人员、临床医生、制药公司和监管机构能够比目前在上市过程中更早地识别主要由新药引起的罕见药物不良反应，从而量化严重不良事件。
