1] Clinical Modeling & Simulation, F. Hoffmann-La Roche Ltd., Basel, Switzerland [2] Current address: Novartis Pharma AG, Postfach, Basel, Switzerland.
Clinical Modeling & Simulation, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
CPT Pharmacometrics Syst Pharmacol. 2014 Jan 2;3(1):e87. doi: 10.1038/psp.2013.63.
A new subcutaneous (s.c.) trastuzumab formulation provides savings in terms of time and is preferred by patients and health care professionals relative to standard intravenous (i.v.) administration due to simpler and more rapid administration (2-5 minutes). Selection of the s.c. dose was based on a pharmacokinetic bridging approach that aimed to achieve noninferior trastuzumab serum trough concentrations (Ctrough) vs. reference i.v. administration. Using population modeling and simulation, we showed that a fixed 600-mg trastuzumab s.c. dose, administered thrice-weekly (Q3W) without a loading dose, would provide Ctrough (predose Cycle 8) and area under the time-concentration curve (AUC0-21 days, Cycle 7) at least as high as Q3W i.v. administration. The model was retrospectively validated using observed pharmacokinetic data from an independent phase III study of (neo)adjuvant trastuzumab (HannaH). These results provide a strong pharmacokinetic rationale for the trastuzumab s.c. 600-mg fixed dose, supported by the noninferior efficacy of this regimen vs. reference i.v. administration.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e87; doi:10.1038/psp.2013.63; advance online publication 2 January 2014.
一种新的皮下（s.c.）曲妥珠单抗制剂在时间上具有优势，与标准静脉内（i.v.）给药相比，由于给药更简单、更迅速（2-5 分钟），因此更受患者和医疗保健专业人员的青睐。s.c.剂量的选择基于药代动力学桥接方法，旨在实现与参考 i.v.给药相比非劣效的曲妥珠单抗血清谷浓度（Ctrough）。通过群体建模和模拟，我们表明，固定的 600mg 曲妥珠单抗 s.c.剂量，无需负荷剂量，每周三次（Q3W）给药，将提供至少与 Q3W i.v.给药一样高的 Ctrough（第 8 周期预剂量）和第 7 周期的时间-浓度曲线下面积（AUC0-21 天）。该模型使用独立的曲妥珠单抗（新）辅助治疗的 III 期研究中的观察到的药代动力学数据进行了回顾性验证（HannaH）。这些结果为曲妥珠单抗 s.c. 600mg 固定剂量提供了强有力的药代动力学依据，支持该方案与参考 i.v.给药相比的非劣效疗效。CPT 药效学系统药理学（2014）3，e87；doi:10.1038/psp.2013.63；2014 年 1 月 2 日在线提前发布。
