一种研究外用产品药代动力学灌注效应的方法。

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Saara K. Luna , M. Alice Maciel Tabosa , Ting Chean Khoo , Conor L. Evans
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引用次数: 0

摘要

局部药物产品被输送到皮肤结构,以治疗许多皮肤疾病。由于皮肤环境和屏障的复杂性,局部药物的药代动力学很难确定,特别是在体内,因为大多数药代动力学评估方法只能在体外进行。值得注意的是,体内条件包括通过真皮毛细血管的灌注,它通过作为清除途径和驱动皮肤渗透的“水槽”来影响局部药物摄取。在这项研究中,我们开发了一种方法来检查灌注对体内局部药物摄取的影响,使用受激拉曼散射(SRS)显微镜,这是一种化学特异性成像方式,非常适合观察局部药物随时间的渗透。在这项初步研究中,我们对配对小鼠耳皮肤在70/30 v/v的Transcutol:EtOH下他扎罗汀的体内和体外摄取进行了成像,比较灌注对他扎罗汀浓度(与SRS信号强度成线性关系)随时间的影响,以及角质层和皮脂腺富脂区和贫脂区药代动力学参数(Tmax、Cmax、AUC)的影响。SRS信号时间趋势的明显变化以及角质层药代动力学参数在体内和体外比较富脂区和贫脂区摄取的统计学差异表明,在没有灌注的情况下,他zarotene通过体外皮肤的通量减慢。灌注和非灌注皮肤富脂区和贫脂区渗透差异反映了灌注时他扎罗汀的渗透速率和去除增加(体内),无灌注时他扎罗汀的渗透速率降低和消除途径缺乏(体外)。我们的方法被证明是有效的评估体内灌注对局部药物摄取的影响,促进更好地理解灌注对局部药物递送的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Developing a method for the study of perfusion effects in topical product pharmacokinetics

Developing a method for the study of perfusion effects in topical product pharmacokinetics
Topical drug products are delivered to skin structures to treat numerous skin diseases. Due to the complexities of the skin environment and barrier, topical drug pharmacokinetics are difficult to determine, especially in vivo, as most pharmacokinetic assessment methods can only be performed ex vivo. Notably, in vivo conditions include perfusion via dermal capillaries, which influences topical drug uptake by acting as a clearance route and a “sink” driving permeation through the skin. In this study, we develop a method to examine the effects of perfusion on topical drug uptake in vivo using stimulated Raman scattering (SRS) microscopy, a chemically-specific imaging modality ideal for visualizing topical drug permeation over time. In this pilot study, we imaged the in vivo and ex vivo uptake of tazarotene in 70/30 v/v Transcutol:EtOH in paired mouse ear skin, comparing the effects of perfusion on tazarotene concentration (linearly proportional to SRS signal intensity) over time and pharmacokinetic parameters (Tmax, Cmax, AUC) in lipid-rich and lipid-poor regions in the stratum corneum and sebaceous glands. Obvious variations in SRS signal-time trends and statistically significant differences in stratum corneum pharmacokinetic parameters comparing uptake in lipid-rich and lipid-poor regions in vivo and ex vivo indicated slowed tazarotene flux through ex vivo skin in the absence of perfusion. The observed permeation differences in lipid-rich and lipid-poor regions in perfused and non-perfused skin reflects increased tazarotene permeation rate and removal in the presence of perfusion (in vivo) and decreased permeation rate and lack of elimination route in the absence of perfusion (ex vivo). Our method is demonstrated to be effective in assessing in vivo perfusion effects on topical drug uptake, promoting a better understanding of the influence of perfusion on topical drug delivery.
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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