糠酸氟替卡松是一种新型吸入性皮质类固醇，与吸入性丙酸氟替卡松相比，在人肺吸收动力学中表现出较长时间。

文章的细节

引用
复制到剪贴板

张志刚，张志刚，张志刚

糠酸氟替卡松是一种新型吸入性皮质类固醇，与吸入性丙酸氟替卡松相比，在人肺吸收动力学中表现出较长时间。

临床药效学杂志。2013年1月;52(1):37-42。doi: 10.1007 / s40262 - 012 - 0021 - x。

PubMed ID
23184737 (PubMed视图
］
摘要

背景:糠酸氟替卡松(FF;GW685698)是一种新型吸入性皮质类固醇，24小时起效，目前正在开发中，可与长效β(2)肾上腺素受体激动剂维兰特罗(GW642444)联合用于慢性阻塞性肺病和哮喘，每日一次。体外研究研究了皮质类固醇的呼吸组织结合特性，结果显示，与其他临床使用的吸入性皮质类固醇相比，FF具有最大的细胞积累和最慢的外排速率，与更大的组织保留相一致。糖皮质激素受体与FF结合的亲和力增强，加上其与组织的联系延长，可能会导致更大、更持久的抗炎作用，并应提供相关的每日一次的疗效。目的:本研究的目的是通过反褶积分析评估三种探索性干粉制剂(通过DISKHALER((R))吸入FF后从肺部全身吸收FF的速率和程度，并与吸入丙酸氟替卡松(FP)[通过DISKHALER((R))]进行比较。方法:这项开放标签、部分随机、六方交叉研究评估了三种早期发育的干粉吸入式FF制剂，通过DISKHALER单次给药((R))。健康男性受试者(n = 24)每人接受FF(2000马克杯;三种配方)，吸入FP(1000杯;通过DISKHALER((R)))和每个分子250杯静脉输注。吸入FF和FP的生物利用度均代表从肺部的吸收，因为吸入剂量吞下部分的口服生物利用度可以忽略不计(< 1.5%)。 To investigate the absorption kinetics from the lung, the inhaled concentration-time data were subjected to deconvolution analysis using derived pharmacokinetic parameters from fitting of the intravenous concentration-time data. RESULTS: The terminal elimination half-life (t((1/2)beta)) for inhaled FF was considerably longer (range 17-24 h) than the t((1/2)beta) estimated for intravenous FF (14 h), whereas t((1/2)beta) for FP was similar whether inhaled or given intravenously (11 and 14 h, respectively). This would suggest that FF is exhibiting absorption rate-limited pharmacokinetics following inhaled FF dosing and that the apparent t((1/2)beta) is an estimate of absorption rate. The lung mean absorption time for FF was approximately 7 h irrespective of formulation, which was considerably longer than FP (2.1 h). The time for 90 % absorption from the lung was significantly longer for FF (20-30 h) than for FP (8 h), indicating a significantly longer lung retention time for FF. CONCLUSION: In comparison with inhaled FP, inhaled FF (independent of formulation) demonstrated prolonged absorption from the lung into the systemic circulation, indicating a longer lung retention time and suggesting the potential for maintained efficacy with once-daily administration.

引用本文的药物库数据

药物