Pitsikas N
Boehringer Ingelheim, Via Lorenzini 8, Milan 20139, Italy.
Curr Opin Investig Drugs. 2000 Sep;1(1):116-21.
Lilly is developing duloxetine, a 5-HT and norepinephrine uptake inhibitor as a potential treatment for depression and urinary incontinence. In Japan, it is being jointly developed with Shionogi [187401]. Phase III trials for depression and phase II trials for urinary incontinence are underway in Japan [296442,328887]. Lilly expects to file for depression in 2002 and phase III trials for urinary incontinence are planned to start enrollment by the end of 2000 [358429,370526,373870]. Duloxetine has a half-life of 10 to 15 h in humans, and parameters reach a steady-state after 3 days of daily administration. In a 6-week, open-label study duloxetine was safe and well tolerated in 79 clinically depressed patients. Clinical response occurred in 78% of patients, and remission occurred in 60%. Insomnia and nausea occurred with an incidence of 20% [300881]. Duloxetine may offer advantages over existing antidepressants, such as Lilly's fluoxetine, because of faster recovery and fewer side effects [190226]. In June 2000, Morgan Stanley Dean Witter predicted duloxetine would reach the market in 2002 with annual sales in this year of US $50 million, rising to $200 million in 2005 [373870]. In February 1999, Deutsche Bank predicted Lilly's sales at US $200 million in 2002 rising to $400 million in 2003 [316821]. In May 2000, Deutsche Bank had made further predictions, stating that filing for duloxetine is expected in the fourth quarter of 2001, and peak sales are expected to exceed US $500 million. Also in February 1999, Lehman Brothers predicted the first major launch date (US and ex-US) to be 2002, with the year of peak sales to be 2008 [319225]. In August 1999, this prediction changed, and the expected launch date became 2001, with an 80% probability of reaching the market and sales peaking at US $150 million in 2012 [349228].
礼来公司正在研发度洛西汀，一种5-羟色胺和去甲肾上腺素摄取抑制剂，作为治疗抑郁症和尿失禁的潜在药物。在日本，它正与盐野义公司联合开发[187401]。日本正在进行抑郁症的III期试验和尿失禁的II期试验[296442,328887]。礼来公司预计2002年提交抑郁症相关申请，尿失禁的III期试验计划于2000年底开始招募患者[358429,370526,373870]。度洛西汀在人体内的半衰期为10至15小时，每日给药3天后各项参数达到稳态。在一项为期6周的开放标签研究中，79名临床抑郁症患者使用度洛西汀安全且耐受性良好。78%的患者出现临床反应，60%的患者病情缓解。失眠和恶心的发生率为20%[300881]。度洛西汀可能比现有的抗抑郁药如礼来公司的氟西汀更具优势，因为恢复更快且副作用更少[190226]。2000年6月，摩根士丹利添惠预测度洛西汀将于2002年上市，当年销售额为5000万美元，2005年将增至2亿美元[373870]。1999年2月，德意志银行预测礼来公司2002年的销售额为2亿美元，2003年将增至4亿美元[3168,21]。2000年5月，德意志银行做出进一步预测，称度洛西汀预计在2001年第四季度提交申请，预计峰值销售额将超过5亿美元。同样在1999年2月，雷曼兄弟预测首次主要上市日期（美国及美国以外地区）为2002年，销售额峰值年份为2008年[3192,25]。1999年8月，这一预测发生变化，预计上市日期变为2001年，进入市场的概率为80%，销售额在2012年达到峰值1.5亿美元[3492,28]。
