Substrate and method dependent inhibition of three ABC-transporters (MDR1, BCRP, and MRP2).

Pedersen JM, Khan EK, Bergström CAS, Palm J, Hoogstraate J, Artursson P

Eur J Pharm Sci 103 (-) 70-76 [2017-05-30; online 2017-03-02]

Drug transport and drug-drug interactions (DDI) with human ABC transporters are generally investigated in mammalian cell lines or inverted membrane vesicles from insect cells (Sf9) overexpressing the transporter of interest. In this study, we instead used membrane vesicles from human embryonic kidney cells (HEK293) overexpressing wild type MDR1/Pgp (ABCB1), BCRP (ABCG2), and MRP2 (ABCC2) with the aim to study the concentration dependent inhibition of shared and prototypic probe substrates. We first investigated 15 substrates and identified estrone-17-beta-glucorinide (E17G) as shared substrate. Nine specific and general inhibitors were then studied using E17G and prototypic probe substrates. The results were compared with those previously obtained in Sf9 vesicles and cell lines of canine (MDCKII) and human (Saos-2) origin. For the majority of inhibitors, K

Affiliated researcher

PubMed 28263911

DOI 10.1016/j.ejps.2017.03.002

Crossref 10.1016/j.ejps.2017.03.002

pii: S0928-0987(17)30134-3

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