@article{oai:kanazawa-u.repo.nii.ac.jp:00013318,
 author = {Ito, Katsuaki and Nguyen, Hai Thien and Kato, Yukio and Wakayama, Tomohiko and Kubo, Yoshiyuki and Iseki, Shoichi and Tsuji, Akira},
 issue = {3},
 journal = {Journal of Controlled Release},
 month = {Nov},
 note = {The purpose of the present study was to investigate the role of P-glycoprotein (P-gp) in drug disposition in skin. The distribution of P-gp substrates (rhodamine 123 and itraconazole) to the skin after administration from the epidermal side was lower in P-gp gene knockout (mdr1a/1b-/-) mice than that in wild-type mice. Coadministration of propranolol, a P-gp inhibitor, decreased the distribution of itraconazole to the skin in wild-type mice, but not in mdr1a/1b-/- mice. These results suggest that P-gp contributes to the influx (from the epidermal side) of its substrates into skin, although P-gp is generally involved in efflux of drugs from various tissues. This finding was supported by the lower vectorial transport of rhodamine 123 from the epidermal to the hypodermal side in mdr1a/1b-/- mice in Ussing-type chamber experiments and by the immunohistochemical localization of P-gp throughout the dermal layer. Distribution of itraconazole after intravenous administration, on the other hand, was higher in mdr1a/1b-/- mice than that in wild-type mice, suggesting that P-gp transports this drug from the skin to the circulation. The present findings are the first to demonstrate involvement of P-gp in dermal drug disposition. © 2008., 金沢大学医薬保健研究域薬学系 金沢大学医薬保健研究域医学系},
 pages = {198--204},
 title = {P-Glycoprotein (Abcb1) is involved in absorptive drug transport in skin},
 volume = {131},
 year = {2008}
}