ATP binding cassette transporters in two distinct compartments of the skin contribute to transdermal absorption of a typical substrate

Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer

“…On the other hand, pharmacokinetic studies have shown that EGFR-TKIs are transported to the skin by ABCG2 (BCRP) and/or ABCC (P-gp) [16,17]. The problem is how inhibition of EGFR causes skin damage.…”

Involvement of the Transporters P-Glycoprotein and Breast Cancer Resistance Protein in Dermal Distribution of the Multikinase Inhibitor Regorafenib and Its Active Metabolites

“…In some experiments, the skin was divided into epidermis and dermis as described previously. 12 To collect bile samples, the gallbladder was cannulated with polyethylene tubing (SP10; Natsume Seisakusho Company, Ltd., Tokyo, Japan), and only bile samples were collected from mice. Cassette dosing of 24 molecularly targeted small molecules was performed by injection of the following 3 mixtures into the jugular vein: (1) a mixture of crizotinib (297 mg/kg), erlotinib (130 mg/kg), gefitinib (148 mg/kg), imatinib (163 mg/kg), pazopanib (28.9 mg/kg), regorafenib (319 mg/kg), sorafenib (153 mg/kg), and sunitinib (132 mg/kg); (2) a mixture of dabrafenib (171 mg/kg), dacomitinib (155 mg/ kg), dasatinib (161 mg/kg), lenvatinib (141 mg/kg), nilotinib (175 mg/ kg), pazopanib (28.9 mg/kg), ponatinib (176 mg/kg), regorafenib (159 mg/kg), trametinib (203 mg/kg), and vandetanib (157 mg/kg); (3) a mixture of afatinib (160 mg/kg), bortezomib (127 mg/kg), cabozantinib (166 mg/kg), carfilzomib (238 mg/kg), lapatinib (192 mg/kg), pazopanib (28.9 mg/kg), regorafenib (159 mg/kg), ruxolitinib (101 mg/ kg), tofacitinib (266 mg/kg), and vemurafenib (162 mg/kg).…”

“…10,11 According to immunohistochemical analyses, both transporters are localized to capillary endothelial cells in both species. 12,13 Distribution of intravenously injected substrates to skin is restricted by these transporters. 12 In addition, both P-gp and BCRP are localized to the basal layer of epidermis keratinocytes.…”

“…12,13 Distribution of intravenously injected substrates to skin is restricted by these transporters. 12 In addition, both P-gp and BCRP are localized to the basal layer of epidermis keratinocytes. 12,13 Interestingly, these transporters have also been proposed to be involved in absorption of their substrates from skin to circulation after topical application, and localization of these transporters in both keratinocytes and endothelial cells may lead to such bidirectional transport.…”

“…12 In addition, both P-gp and BCRP are localized to the basal layer of epidermis keratinocytes. 12,13 Interestingly, these transporters have also been proposed to be involved in absorption of their substrates from skin to circulation after topical application, and localization of these transporters in both keratinocytes and endothelial cells may lead to such bidirectional transport. 12,14 However, information on the possible role of these transporters in the skin is still quite limited.…”