利用基于模型的模拟来优化普罗利德6个月肌内储存配方的延长剂量
Li-Feng Hsu1,2,3,4
1School of Pharmacy, National Defense Medical Center, Taipei, Taiwan. Lfhsu@cde.org.tw.
European journal of drug metabolism and pharmacokinetics
|January 29, 2025
概括
延长六个月内肠道内存注射的普罗立德剂量间隔显示出前列腺癌治疗的前景. 每8个月或9个月一次的疗法可以维持抑制,简化患者的护理.
科学领域:
- 药理学和药物输送 药理学和药物输送
- 瘤学和泌尿病学 在线咨询
- 临床试验模拟的临床试验
背景情况:
- 像普罗莱德这样的淋巴激素释放激素 (GnRH) 激动剂对于抑制前列腺癌管理中的丸激素至关重要.
- 长效配方,如6个月肌内 (IM) 普罗化储存,提高了患者的便利性和治疗坚持.
- 优化剂量间隔是平衡治疗疗效与以患者为中心的护理的关键.
研究的目的:
- 为了评估延长剂量间隔的效果,在前列腺癌治疗中使用六个月的leuprolide IM depot配方.
- 为了确定延长的治疗方案是否可以在90%以上的患者中保持丸激素水平低于割值 (<0.5 ng/ml和<0.2 ng/ml).
主要方法:
- 使用经过验证的药理动力学/药理动力学模型来模拟的抑制.
- 模拟延长剂量方案:每6个月,7个月,8个月,9个月,10个月,11个月和12个月 (Q6M-Q12M) 在1000个虚拟对象中.
- 对基线丸激素和药物吸收变异性进行了敏感性分析.
主要成果:
- 模拟表明,将间隔延长到Q8M,在90%以上的受试者中保持丸激素<0.2 ng/ml.
- 将间隔延长到Q9M,在90%以上的受试者中,维持丸激素<0.5 ng/ml.
- 敏感性分析证实了这些延长剂量方案的稳定性.
结论:
- 延长六个月的leuprolide IM仓库配方的剂量间隔超过6个月是可行的.
- Q8M和Q9M方案是减少注射频率的可行选择,同时保持治疗疗效.
- 需要进一步的临床研究来证实这些延长剂量策略的长期疗效.
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