Involvement of organic anion transport system in transdermal absorption of flurbiprofen
Involvement of organic anion transport system in transdermal absorption of flurbiprofen
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DOI：
10.1016/j.jconrel.2007.08.019
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发表时间：
2007-12-04
影响因子：
10.8
通讯作者：
Tsuji, Akira
中科院分区：
文献类型：
--
作者：
Ito, Katsuaki;Kato, Yukio;Tsuji, Akira
我们先前证明氟比洛芬的经皮渗透是由非线性转运机制介导的。在这里，我们的目的是表征这种运输机制，采用一个Ussing-type室的方法与胶带剥离无毛小鼠皮肤。[H-3]氟吡泊芬的经皮渗透是矢量的，饱和的和能量依赖性的，这表明载体介导的运输系统的参与。[H-3]氟比洛芬的经皮渗透和从表皮侧的摄取受到各种非甾体抗炎药（NSAID）的抑制。抑制效力与亲脂性没有很好的相关性;阴离子NSAID往往比非阴离子NSAID更有效的抑制剂。对于给定的阴离子化合物，[H-3]氟比洛芬渗透和摄取的抑制曲线以及米氏常数相似。这些结果表明，在氟比洛芬透皮吸收过程中，一个有机阴离子转运系统参与了从表皮侧的氟比洛芬摄取。流出的[H-3]氟比洛芬从皮肤到表皮侧，但不是皮下侧，氟比洛芬或几种阴离子化合物的存在下增加。这种反式刺激可能表明有机阴离子交换系统的参与。有机阴离子转运蛋白2（OAT 2）是参与皮肤吸收和/或外排氟比洛芬的交换剂的候选者。(c)2007 Elsevier B. V.保留所有权利。
We previously demonstrated that transdermal permeation of flurbiprofen is mediated by a nonlinear transport mechanism(s). Here, we aimed to characterize this transport mechanism by employing an Ussing-type chamber method with tape-stripped hairless mouse skin. Transdermal permeation of [H-3]flurbipofen was vectorial, saturable and energy-dependent, suggesting the involvement of a carrier-mediated transport system. Transdermal permeation and uptake from the epidermal side of [H-3]flurbiprofen were inhibited by various nonsteroidal anti-inflammatory drugs (NSAIDs). The inhibitory potency did not correlate well with lipophilicity; anionic NSAIDs tended to be more potent inhibitors than non-anionic NSAIDs. The inhibition profile of both [H-3]flurbiprofen permeation and uptake, and the Michaelis constants, were similar for a given anionic compound. These results suggest that an organic anion transport system is involved in flurbiprofen uptake from the epidermal side during the process of transdermal absorption. Efflux of [H-3]flurbiprofen from the skin to the epidermal side, but not to the hypodermal side, increased in the presence of flurbiprofen or several anionic compounds. Such trans-stimulation may suggest the involvement of an organic anion exchanger system. Organic anion transporter 2 (OAT2) is a candidate for the exchanger involved in uptake and/or efflux of flurbiprofen in the skin. (c) 2007 Elsevier B.V. All rights reserved.