Leopold Claudia S
Department of Pharmacy--Pharmaceutical Technology, University of Leipzig, Leipzig, Germany.
Eur J Pharm Biopharm. 2003 Jul;56(1):53-8. doi: 10.1016/s0939-6411(03)00045-6.
The FDA (Food and Drug Administration) Guidance for Industry 'Topical Dermatologic Corticosteroids: In vivo Bioequivalence' describes two methods for evaluation of cutaneously applied corticosteroid formulations by measurement of the skin blanching response with a chromameter. The experimental options are: staggered application with synchronized removal or synchronized application with staggered removal. From the resulting response vs. time profiles, the areas under the effect curves (AUECs) are calculated and plotted as a function of the exposure time period to obtain dose/response-like relationships. If these experimental procedures are analyzed pharmacokinetically applying the Bateman equation and Fick's First Law of diffusion, several critical factors may be determined that need to be considered in order to avoid misinterpretation of the data. If solution-type preparations are investigated, the applied formulation volume should be the same on all application sites. In the case of suspension-type preparations, the applied drug dose is not critical. Moreover, it is essential to guarantee zero order kinetics during the application time periods, which may only be achieved with suspension-type preparations or a sufficiently high volume of solution-type preparations. If all these critical factors are taken care of, bioavailability factors (solutions) and enhancement factors (suspensions) may be calculated as the quotient of the AUECs of test and reference formulations.
美国食品药品监督管理局（FDA）的行业指南《局部用皮质类固醇：体内生物等效性》描述了两种通过使用色差仪测量皮肤变白反应来评估经皮应用皮质类固醇制剂的方法。实验选项为：交错给药并同步去除或同步给药并交错去除。从所得的反应与时间曲线中，计算效应曲线下的面积（AUECs），并将其绘制为暴露时间段的函数，以获得类似剂量/反应的关系。如果应用贝特曼方程和菲克第一扩散定律对这些实验程序进行药代动力学分析，则可以确定几个关键因素，为避免数据误解需要对这些因素加以考虑。如果研究溶液型制剂，所有给药部位的制剂体积应相同。对于混悬型制剂，给药剂量并不关键。此外，在给药时间段内保证零级动力学至关重要，这只有通过混悬型制剂或足够大量的溶液型制剂才能实现。如果所有这些关键因素都得到关注，生物利用度因子（溶液）和增强因子（混悬液）可以计算为受试制剂和参比制剂的AUECs之商。
