芬太尼的皮下（SC）给药可以快速调整剂量，以治疗与癌症相关的紧急疼痛。确定最佳芬太尼剂量后，患者通常会转向使用透皮 (TD) 芬太尼贴剂。使用贴剂后继续 SC 芬太尼长达 12 小时会导致芬太尼浓度升高和芬太尼相关毒性。基于这些发现以及使用药代动力学 (PK) 模型的模拟，在使用贴剂后立即停止 SC 芬太尼给药。通过评估轮换前后芬太尼暴露的 PK 等效性来验证芬太尼轮换时间表。PK 样本和前瞻性收集接受芬太尼轮换的癌症相关疼痛患者从轮换前 12 小时到轮换后 12 小时的临床数据。2021 年 12 月至 2023 年 9 月期间，29 名可评估患者纳入该研究。旋转后与旋转前曲线下面积 (AUC) 之间的几何平均比率的 90% 置信区间 (CI) 落在预先指定的 0.8 - 1.25 等价区间内 (90% CI: 1.05 - 1.16)。患者报告的恶心（p=0.047）和蒸腾（p=0.034）强度在旋转后均下降。旋转前后的疼痛强度和其他不良事件没有显着差异。由于芬太尼相关毒性，一名患者需要在轮换后 40 小时调整阿片类药物治疗。更新的轮换方案意味着 1:1 剂量转换并在轮换后立即停止 SC 芬太尼，导致轮换前后芬太尼暴露量相等。此外，该给药方案在轮换期间被证明是安全有效的。从 SC 芬太尼转向 TD 芬太尼时的新剂量方案可以在常规姑息治疗中有效、安全地实施。版权所有 © 2024。由 Elsevier Inc. 出版。

Subcutaneous (SC) administration of fentanyl allows for rapid dose titration to treat urgent cancer-related pain. After establishing the optimal fentanyl dose, patients typically rotate towards transdermal (TD) fentanyl patches. Continuing the SC fentanyl up to 12h after application of the patch led to elevated fentanyl concentrations and fentanyl-related toxicities. Based on these findings, and simulations using a pharmacokinetic (PK) model, SC fentanyl administration was discontinued immediately following the application of the patch.To validate the fentanyl rotation schedule by assessing the PK equivalence in fentanyl exposure before and after rotation.PK samples and clinical data were prospectively collected from 12 hours prior to rotation until 12 hours after rotation in patients with cancer-related pain undergoing fentanyl rotation.Between December 2021 and September 2023, 29 evaluable patients were enrolled in the study. The 90% confidence interval (CI) of the geometric mean ratio between the post- over pre-rotation area under the curve (AUC) fell within the prespecified 0.8 - 1.25 equivalence interval (90% CI: 1.05 - 1.16). Patient-reported intensity of both nausea (p = 0.047) and transpiration (p= 0.034) decreased post-rotation. Pain intensity and other adverse events did not differ significantly pre- and post-rotation. One patient needed adjustment of opioid therapy 40 hours after rotation due to fentanyl-related toxicities.The updated rotation scheme, implying a 1:1 dose conversion and discontinuation of SC fentanyl directly after rotation, resulted in equivalent fentanyl exposure pre- and post-rotation. Moreover, the dosing regimen showed to be safe and efficacious during rotation. The new dosing regimen when rotating from SC to TD fentanyl can be effectively and safely implemented in routine palliative care.Copyright © 2024. Published by Elsevier Inc.