孙忠实：如何实现真正意义的个体化给药.ppt

42 SSRIs增加自杀意念 最近相继有报告认为,SSRI可一增加患者尤其是年青患者自杀意念的趋势，为此,FDA提出对此类药进行重新评估 (Mkt 2003;30:23) 最新报告,新型选择性SSRI抗抑郁药度洛西汀导致健康受试者自杀5例(共100例受试者),FDA将调查与评估此事件。 另有20个安慰剂对照试验表明,有8种SSRIs可增加自杀的危险性,其中以氟西汀RR1.16,帕罗西汀RR1.29为著，因此,于2003,10,27,FDA要求在瓶签上加警告语：强调必须逐渐增量，不能突然停药，密切观察,尤其是用药的1~9天,高危患者，18岁以下慎用。 JAMA 2004;292:338~381 慎用EPO 警戒抗病毒药致心肌梗死 Class of Antiretroviral Drugs and the Risk of Myocardial Infarction Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group Methods We analyzed data collected through February 2005 from our prospective observational study of 23,437 patients infected with the human immunodeficiency virus. The incidence rates of myocardial infarction during the follow-up period were calculated, and the associations between myocardial infarction and exposure to protease inhibitors or nonnucleoside reverse-transcriptase inhibitors were determined N Engl J Med 2007;356:1723~1735 蛋白酶抑制剂:利托拉韦,茚地拉韦; 非核苷逆转录酶抑制剂:奈韦拉平,地拉韦平 双膦酸盐致眼病 截止2003.10所致眼病约有40种，主要病症是炎症、白内障、角膜溃疡、角膜-结膜炎、青光眼、眼痛、视力异常等。发生率最高的是阿仑膦酸钠(Alendrnate Sodium)，共发生374例,其中不少病例系并用药物。其次为 依班膦酸钠Ibundronate Sodium 3例 氯膦酸钠 Clodronate Sodium 9例 依替膦酸钠Etidronate Sodium 35例 帕米膦酸钠Pamidronate Sodium 132例 利噻膦酸钠Risedronate Sodium 69例 替奴膦酸钠 Tiludronate Sodium 2例 唑来膦酸钠 Zoledronate Sodium 25例 启迪之五:抓住源头 防患未然 Scientific and Regulatory Aspects of Quality Control for Drugs Begin Drug Development with Quality by Design (QbD) Approach. Stephen Miller, Ph.D. Office of New Drug Quality Assessment Center for Drug Evaluation and Research, FDA Stephen.Miller@fda.hhs.gov. June 26, 2006 “质量源于设计” 具体措施之一: 新药开发越来越难 开发新药过程中的淘汰率 真正的NMEs很少 基因组学加快新药的研发 FDA1996~2008批准的新药呈下降趋势 FDA1997~2007批准的新药呈下降趋势 Barcode 启迪之四:开展基因组学研究━实现真正意义的个体化给药 关于基因多态性 P450的基因(遗传)多态性（Genetic polymorphisms）使药物代谢存在着种族和个体差异，尤其是CYP2C19和2D6。