Evaluation of Bioequivalence and Pharmacokinetic Profiles for Topical Desonide Cream Using Chinese Skins.

IF 2.8 4区医学 Q2 DERMATOLOGY

Skin Pharmacology and Physiology Pub Date : 2024-08-19 DOI:10.1159/000540782

Yuanyuan Sun, Nan Yang, Jie Huang, An Yao, Ling Ye, Shuang Yang, Min Xiao, Xuqing Zhang, Jinsong Ding, Yun Kuang, Yali Zhou, Guoping Yang

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引用次数: 0

Abstract

Introduction: Skin-blanching assay has been established as a surrogate method for assessing bioequivalence of topical corticosteroids. This study aimed to apply the skin-blanching assay to evaluate the bioequivalence of a test desonide cream (T) compared with the reference Desonide® (R) using Chinese skins. Additionally, the pharmacokinetics and safety profiles were also assessed.

Methods: By detecting the degree of skin blanching under different dose durations in a pilot dose-duration-response study, the area under the observed effect-time curve (AUEC) and half of the maximum effect (ED50) was calculated. Based on this, the skin color of different time points after a dose duration of ED50, D1 (0.5 × ED50), and D2 (2 × ED50) were detected as a pharmacodynamic indicator to compare between test and reference creams. Single-center, single-dose, randomized, open-label, two-cycle crossover pharmacokinetic studies were designed to make sure the exposure of tested formulationswas not higher than that of the reference formulations. Subjects experiencing adverse events (AEs) were monitored and utilized for safety analysis.

Results: These studies involved 12 subjects for the dose-duration-response study, 100 subjects for the bioequivalence study, and 12 subjects for the pharmacokinetic study. The results showed that the population ED50 was 0.88 ± 0.45 h; the mean ratio of area under effective curve from 0 to 24 h (AUEC0-24h) of test and reference preparations was 0.95, with a 90% confidence interval as 88.09-101.72%, indicating the bioequivalence of the test formulation and Desonide®. The maximum plasma concentration (Cmax) and area under the concentration time curve from time 0 to the last time point (AUC0-t) of T and R were 20.8 ± 11.5 pg/mL versus 19.7 ± 10.1 pg/mL, respectively, and 451.04 ± 363.65 pgh/mL versus 541.47 ± 581.41 pgh/mL, respectively. The systemic exposure of a single dose of the test cream was not higher than that of the reference preparation. All of the volunteers experienced grade 1 AEs, suggesting that single administration of the test desonide cream is well tolerated in the Chinese healthy population.

Conclusions: This study demonstrated the applicability of skin-blanching assay in Chinese skins and established the bioequivalence of test and reference desonide creams.

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用中国人的皮肤评价外用地索奈德乳膏的生物等效性和药代动力学特征。

简介皮肤灼伤试验已被确定为评估外用皮质类固醇生物等效性的替代方法。本研究旨在使用中国人的皮肤，采用皮肤灼热试验来评估试验用的地索奈德乳膏（T）与参考用的地索奈德®（R）的生物等效性。此外，还对药代动力学和安全性进行了评估：方法：在一项剂量-持续时间-反应试验研究中，通过检测不同剂量持续时间下的皮肤褪色程度，计算了观察效应时间曲线下面积（AUEC）和最大效应的一半（ED50）。在此基础上，检测了 ED50、D1（0.5×ED50）和 D2（2×ED50）剂量持续时间后不同时间点的皮肤颜色，作为药效学指标来比较试验药膏和参考药膏。为了确保受试制剂的暴露量不高于参比制剂，我们设计了一项单中心、单剂量、随机、开放标签、两周期交叉药代动力学研究。对出现不良事件（AEs）的受试者进行了监测，并用于安全性分析：这些研究中，12 名受试者参与了剂量-持续时间-反应研究，100 名受试者参与了生物等效性研究，12 名受试者参与了药代动力学研究。结果表明，受试者的 ED50 为 0.88±0.45 h，受试制剂与参比制剂的有效曲线下面积（AUEC0-24h）的平均比值为 0.95，90% 置信区间为 88.09%-101.72%，表明受试制剂与得生泰®具有生物等效性。T和R的最大浓度（Cmax）和暴露量（AUC0-t）分别为20.8 ± 11.5 pg/mL和19.7 ± 10.1 pg/mL，以及451.04 ± 363.65 pg∙h/mL 和541.47 ± 581.41 pg∙h/mL 。单剂量试验乳膏的全身暴露量并不比参比制剂高。所有志愿者都出现了一级不良反应（AEs），这表明中国健康人群对单次给药的地索奈德乳膏具有良好的耐受性：本研究证明了皮肤灼热试验在中国人皮肤中的适用性，并确定了供试制剂和参比制剂的生物等效性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Skin Pharmacology and Physiology 医学-皮肤病学

CiteScore

5.20

自引率

7.40%

发文量

审稿时长

>12 weeks

期刊介绍： In the past decade research into skin pharmacology has rapidly developed with new and promising drugs and therapeutic concepts being introduced regularly. Recently, the use of nanoparticles for drug delivery in dermatology and cosmetology has become a topic of intensive research, yielding remarkable and in part surprising results. Another topic of current research is the use of tissue tolerable plasma in wound treatment. Stimulating not only wound healing processes but also the penetration of topically applied substances into the skin, this novel technique is expected to deliver very interesting results.