Bashaw Edward Dennis, Tran Doanh C, Shukla Chinmay G, Liu Xiaomei
US Food and Drug Administration, Silver Spring, MD, USA.
Ther Innov Regul Sci. 2015 Jan;49(1):108-115. doi: 10.1177/2168479014539157. Epub 2014 Jun 27.
Dermatologic diseases can present in varying forms and severity, ranging from the individual lesion and up to almost total skin involvement. Pharmacokinetic assessment of topical drug products has previously been plagued by bioanalytical assay limitations and the lack of a standardized study design. Since the mid-1990's the US Food and Drug Administration has developed and implemented a pharmacokinetic maximal usage trial (MUsT) design to help address these issues. The MUsT design takes into account the following elements: the enrollment of patients rather than normal volunteers, the frequency of dosing, duration of dosing, use of highest proposed strength, total involved surface area to be treated at one time, amount applied per square centimeter, application method and site preparation, product formulation, and use of a sensitive bioanalytical method that has been properly validated. This paper provides a perspective of pre-MUsT study designs and a discussion of the individual elements that make up a MUsT.
皮肤病的表现形式和严重程度各不相同，从单个皮损到几乎累及全身皮肤。局部用药品的药代动力学评估此前一直受到生物分析检测局限性以及缺乏标准化研究设计的困扰。自20世纪90年代中期以来，美国食品药品监督管理局已制定并实施了药代动力学最大用量试验（MUsT）设计，以帮助解决这些问题。MUsT设计考虑了以下因素：纳入患者而非正常志愿者、给药频率、给药持续时间、使用最高推荐强度、一次治疗的受累总面积、每平方厘米的用药量、用药方法和部位准备、产品剂型，以及使用经过适当验证的灵敏生物分析方法。本文提供了MUsT前研究设计的观点，并对构成MUsT的各个要素进行了讨论。
