在生物等效性接受标准中纳入治疗窗信息。
Including information on the therapeutic window in bioequivalence acceptance.
作者信息
Jacobs Tom, De Ridder Filip, Rusch Sarah, Van Peer Achiel, Molenberghs Geert, Bijnens Luc
机构信息
Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Universiteit Hasselt, and Katholieke Universiteit Leuven, Belgium, Agoralaan 1, B3590 Diepenbeek, Belgium.
出版信息
Pharm Res. 2008 Nov;25(11):2628-38. doi: 10.1007/s11095-008-9680-6. Epub 2008 Jul 18.
PURPOSE
A novel bioequivalence limit is proposed taking into account the therapeutic window.
METHODS
The therapeutic range is introduced as the ratios maximum tolerated dose/therapeutic dose (MTD/D) and the therapeutic dose/lowest effective dose. The performance of the new acceptance range was compared with the methods of Schuirmann and Karalis. The method was retrospectively applied to data of three drugs with a narrow therapeutic window (phenytoin, theophylline and digoxin).
RESULTS
Simulations and examples show that the resulting bioequivalence limits are (1) narrow for narrow-index drugs, (2) expanded for highly variable drugs with a wide therapeutic window and (3) similar to the classical limits for less variable drugs with a wide therapeutic range.
CONCLUSIONS
The approach has the desirable property of resulting in a more narrow acceptance range for doses near the boundaries of the therapeutic window and a wider acceptance range for products with a broad therapeutic window.
目的
考虑治疗窗，提出一种新的生物等效性限度。
方法
引入治疗范围作为最大耐受剂量/治疗剂量（MTD/D）以及治疗剂量/最低有效剂量的比值。将新接受范围的性能与舒尔曼法和卡拉利斯法进行比较。该方法被回顾性应用于三种治疗窗窄的药物（苯妥英、茶碱和地高辛）的数据。
结果
模拟和实例表明，所得生物等效性限度为：（1）窄治疗指数药物的限度较窄；（2）治疗窗宽的高变异药物的限度扩大；（3）治疗范围宽的低变异药物的限度与经典限度相似。
结论
该方法具有理想的特性，即对于接近治疗窗边界的剂量，接受范围更窄；对于治疗窗宽的产品，接受范围更宽。
Zotero 插件