P-Glycoprotein in skin contributes to transdermal absorption of topical corticosteroids

Publication date: 15 April 2017 Source:International Journal of Pharmaceutics, Volume 521, Issues 1–2 Author(s): Naoto Hashimoto, Noritaka Nakamichi, Erina Yamazaki, Masashi Oikawa, Yusuke Masuo, Alfred H. Schinkel, Yukio Kato ATP binding cassette transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), are expressed in skin, but their involvement in transdermal absorption of clinically used drugs remains unknown. Here, we examined their role in transdermal absorption of corticosteroids. Skin and plasma concentrations of dexamethasone after dermal application were reduced in P-gp and BCRP triple-knockout (Mdr1a/1b/Bcrp−/− ) mice. The skin concentration in Mdr1a/1b/Bcrp−/− mice was reduced in the dermis, but not in the epidermis, indicating that functional expression of these transporters in skin is compartmentalized. Involvement of these transporters in dermal transport of dexamethasone was also supported by the observation of a higher epidermal concentration in Mdr1a/1b/Bcrp−/− than wild-type mice during intravenous infusion. Transdermal absorption after dermal application of prednisolone, but not methylprednisolone or ethinyl estradiol, was also lower in Mdr1a/1b/Bcrp−/− than in wild-type mice. Transport studies in epithelial cell lines transfected with P-gp or BCRP showed that dexamethasone and prednisolone are substrates of P-gp, but are minimally transported by BCRP. Thus, our findings suggest that P-gp is involved in tr...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research