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ADMET and DMPK, Vol. 3. No. 1., 2015.

Original scientific paper

https://doi.org/10.5599/admet.3.1.163

Characterization of SLC transporters in human skin

Marion Alriquet ; Galderma R&D, les Templiers , 2400 route des Colles, BP 87, F - 06902 Sophia - Antipolis
Karine Sevin ; Galderma R&D, les Templiers , 2400 route des Colles, BP 87, F - 06902 Sophia - Antipolis
Alexandre Gaborit ; Galderma R&D, les Templiers , 2400 route des Colles, BP 87, F - 06902 Sophia - Antipolis
Pierre Comby ; Galderma R&D, les Templiers , 2400 route des Colles, BP 87, F - 06902 Sophia - Antipolis
Bernard Ruty ; Galderma R&D, les Templiers , 2400 route des Colles, BP 87, F - 06902 Sophia - Antipolis
Hanan Osman - Ponchet ; Galderma R&D, les Templiers , 2400 route des Colles, BP 87, F - 06902 Sophia - Antipolis

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Abstract

Most identified drug transporters belong to the ATP-binding Cassette (ABC) and Solute Carrier (SLC) families. Recent research indicates that some of these transporters play an important role in the absorption, distribution and excretion of drugs, and are involved in clinically relevant drug-drug interactions for systemic drugs. However, very little is known about the role of drug transporters in human skin in the disposition of topically applied drugs and their involvement in drug-drug interactions. The aim of this work was to compare the expression in human skin (vs human hepatocytes and kidney) of SLC transporters included in the EMA guidance as the most likely clinical sources of drug interactions. The expression of SLC transporters in human tissues was analyzed by quantitative RT-PCR. Modulation of SLC47A1 and SLC47A2 (MATE1 and MATE2) expression was analyzed after treatment of human skin in organ-culture with rifampicin and UV irradiation. The expression of SLCO2B1 (OATPB), SLCO3A1 (OATPD), SLCO4A1 (OATPE), SLC47A1 and SLC47A2 (MATE1 and MATE2) was detected in human skin, OATPE and MATE1 being the most expressed. OATPE is about 70 times more expressed in human skin than in human hepatocytes. Moreover, the expression of SLC47A1 and SLC47A2 was down-regulated after treatment with rifampicin or after exposure to UV light. The present findings demonstrate that SLCO4A1 (OATPE) and SLC47A1 (MATE1) are highly expressed in human skin and suggest the involvement of SLC transporters in the disposition of topically applied drugs.

Keywords

Solute-carrier transporter; MATE1; UV light; Skin absorption

Hrčak ID:

137562

URI

https://hrcak.srce.hr/137562

Publication date:

31.3.2015.

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