Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
United States Food and Drug Administration, CDER, Office of Pharmaceutical Quality, Silver Spring, MD, USA.
AAPS PharmSciTech. 2020 Apr 16;21(3):117. doi: 10.1208/s12249-020-01658-4.
To estimate strength of a scopolamine transdermal delivery system (TDS) in vivo, using residual drug vs. pharmacokinetic analyses with the goal of scientifically supporting a single and robust method for use across the dosage form and ultimately facilitate the development of more consistent and clinically meaningful labeling. A two-arm, open-label, crossover pharmacokinetic study was completed in 26 volunteers. Serum samples were collected and residual scopolamine was extracted from worn TDS. Delivery extent and rate were estimated by (1) numeric deconvolution and (2) steady-state serum concentration determined from graphical and non-compartmental analyses. In residual drug analyses, mean ± SD scopolamine release rate was 0.015 ± 0.002 mg/h (11% RSD), vs. 0.016 ± 0.006 mg/h (35% RSD) from numeric deconvolution, 0.015 ± 0.005 mg/h (34% RSD) from graphical analysis, and 0.015 ± 0.007 mg/h (44% RSD) from non-compartmental analysis. In residual drug analyses, total drug released was 1.09 ± 0.11 mg (10% RSD), vs. 1.12 ± 0.40 mg (35% RSD) from numeric deconvolution, 1.07 ± 0.35 mg (33% RSD) from graphical analysis, and 1.07 ± 0.45 (42% RSD) from non-compartmental analysis. Extent and rate of scopolamine release were comparable by both approaches, but pharmacokinetic analysis demonstrated greater inter-subject variability.
为了估计莨菪碱透皮给药系统（TDS）在体内的强度，采用残留药物与药代动力学分析相结合的方法，目标是科学支持单一且稳健的方法，适用于整个剂型，并最终促进更一致和更有临床意义的标签的开发。在 26 名志愿者中完成了一项两臂、开放标签、交叉药代动力学研究。采集血清样本，并从佩戴的 TDS 中提取残留的莨菪碱。通过（1）数值反卷积和（2）从图形和非房室分析确定的稳态血清浓度来估计输送程度和速率。在残留药物分析中，平均 ± SD 莨菪碱释放率为 0.015 ± 0.002 mg/h（11% RSD），而数值反卷积为 0.016 ± 0.006 mg/h（35% RSD），图形分析为 0.015 ± 0.005 mg/h（34% RSD），非房室分析为 0.015 ± 0.007 mg/h（44% RSD）。在残留药物分析中，释放的总药物量为 1.09 ± 0.11 mg（10% RSD），而数值反卷积为 1.12 ± 0.40 mg（35% RSD），图形分析为 1.07 ± 0.35 mg（33% RSD），非房室分析为 1.07 ± 0.45 mg（42% RSD）。两种方法的莨菪碱释放程度和速率相当，但药代动力学分析显示出更大的个体间变异性。
