Biopharmaceutics Research Institute, Rhodes University, Grahamstown 6139, South Africa.
Biostudy Solutions LLC, Wilmington, North Carolina 28401, United States.
Mol Pharm. 2022 Aug 1;19(8):2900-2906. doi: 10.1021/acs.molpharmaceut.2c00254. Epub 2022 Jun 28.
The widespread use of topical corticosteroids (TCs) in dermatotherapy requires a consideration of their potency and benefit/risk ratios. Although there are a variety of topical corticosteroid products (TCPs) available on the market and their potencies are ranked using different classification systems, to our knowledge, no classification system to rank the inherent potencies of TC active pharmaceutical ingredients (APIs) currently exists. Most of the published classification systems for TCPs are based on randomized clinical comparative studies and/or vasoconstrictor assay (VCA) data. The objective was to apply the US FDA's VCA to classify the inherent potencies of several TCs using standardized doses to make appropriate comparisons of the relevant APIs in solutions of the same molar concentrations. Six TC APIs were assessed for their relative potencies using healthy human participants. The model was used to fit skin blanching data following application of the respective TCs, and the parameters, and , were derived. values were used as the metric to assess potency. Statistical analyses of the data revealed that the inherent potencies of fluticasone propionate, mometasone furoate, and hydrocortisone butyrate were similar. However, there was no significant difference between hydrocortisone butyrate and clobetasol propionate, while there was a significant difference between clobetasol propionate, fluticasone propionate, and mometasone furoate. Hence, the potency of hydrocortisone butyrate appears to overlap two potency classes. Furthermore, the potencies of betamethasone valerate and methylprednisolone aceponate were similar but lower than those of all of the other APIs. The application of the VCA to classify inherent potency provides a reliable method to establish a classification system for TCs. Inherent potency assessment of TCs provides information that will be useful when choosing an appropriate TC for the development of a TCP for a specific clinical indication.
在皮肤病治疗中广泛使用局部皮质类固醇（TCs）需要考虑其效力和获益/风险比。尽管市场上有多种局部皮质类固醇产品（TCPs），并且它们的效力使用不同的分类系统进行了分类，但据我们所知，目前尚无用于对 TC 活性药物成分（APIs）的固有效力进行分类的分类系统。大多数已发表的 TCP 分类系统都是基于随机临床试验比较研究和/或血管收缩剂测定（VCA）数据。目的是应用美国 FDA 的 VCA 对几种 TC 的固有效力进行分类，使用标准化剂量，以便在相同摩尔浓度的溶液中对相关 APIs 进行适当比较。使用健康的人类参与者评估了六种 TC API 的相对效力。该模型用于拟合各自 TC 应用后的皮肤变白数据，并得出参数 、 和 。 值被用作评估效力的指标。对数据的统计分析表明，丙酸氟替卡松、糠酸莫米松和丁酸氢化可的松的固有效力相似。然而，丁酸氢化可的松和氯倍他索丙酸酯之间没有显著差异，而氯倍他索丙酸酯、丙酸氟替卡松和糠酸莫米松之间存在显著差异。因此，丁酸氢化可的松的效力似乎重叠了两个效力类别。此外，戊酸倍他米松和醋酸甲泼尼龙的效力相似，但低于所有其他 API 的效力。应用 VCA 对固有效力进行分类提供了一种可靠的方法来建立 TC 的分类系统。TC 的固有效力评估提供了在为特定临床适应症开发 TCP 时选择适当 TC 的有用信息。
