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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 [(3)H]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 [(3)H]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 [(3)H]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 [(3)H]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.

Citation

Katsuaki Ito, Yukio Kato, Hiroyuki Tsuji, Hai Thien Nguyen, Yoshiyuki Kubo, Akira Tsuji. Involvement of organic anion transport system in transdermal absorption of flurbiprofen. Journal of controlled release : official journal of the Controlled Release Society. 2007 Dec 4;124(1-2):60-8

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PMID: 17884233

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