RT info:eu-repo/semantics/article
T1 Role of the Abcg2 transporter in plasma levels and tissue accumulation of the anti-inflammatory tolfenamic acid in mice
A1 Blanco Paniagua, Esther
A1 García-Lino, Alba M.
A1 García-Mateos, Dafne
A1 Merino Peláez, Gracia
A1 Álvarez de Felipe, Ana Isabel
A2 Fisiologia
K1 Fisiología
K1 ABCG2
K1 Transport
K1 Plasma levels
K1 Tissue distribution
K1 Tolfenamic acid
K1 2411 Fisiología Humana
AB [EN] The Breast Cancer Resistance Protein (BCRP/ABCG2) is an ATP-binding cassette efflux transporter that is expressed in the apical membrane of cells from relevant tissues involved in drug pharmacokinetics such as liver, intestine, kidney, testis, brain and mammary gland, among others. Tolfenamic acid is an anti-inflammatory drug used as an analgesic and antipyretic in humans and animals. Recently, tolfenamic acid has been repurposed as an antitumoral drug and for use in chronic human diseases such as Alzheimer. The aim of this work was to study whether tolfenamic acid is an in vitro Abcg2 substrate, and to investigate the potential role of Abcg2 in plasma exposure, secretion into milk and tissue accumulation of this drug. Using in vitro transepithelial assays with cells transduced with Abcg2, we showed that tolfenamic acid is an in vitro substrate of Abcg2. The in vivo effect of this transporter was tested using wild-type and Abcg2−/− mice, showing that after oral and intravenous administration of tolfenamic acid, its area under the plasma concentration-time curve in Abcg2−/− mice was between 1.7 and 1.8-fold higher compared to wild-type mice. Abcg2−/− mice also showed higher liver and testis accumulation of tolfenamic acid after intravenous administration. In this study, we demonstrate that tolfenamic acid is transported in vitro by Abcg2 and that its plasma levels as well as its tissue distribution are affected by Abcg2, with potential pharmacological and toxicological consequences.
PB Elsevier
SN 0009-2797
LK http://hdl.handle.net/10612/14180
UL http://hdl.handle.net/10612/14180
NO Blanco-Paniagua, E., García-Lino, A. M., García-Mateos, D., Álvarez, A. I., & Merino, G. (2021). Role of the Abcg2 transporter in plasma levels and tissue accumulation of the anti-inflammatory tolfenamic acid in mice. Chemico-Biological Interactions, 345. https://doi.org/10.1016/J.CBI.2021.109537
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 26-abr-2024