Role of the Abcg2 transporter in plasma levels and tissue accumulation of the anti-inflammatory tolfenamic acid in mice

The Breast Cancer Resistance Protein (BCRP/ABCG2) is an ATP-binding cassette efflux transporter that expressed in the apical membrane of cells from relevant tissues involved drug pharmacokinetics such as liver, intestine, kidney, testis, brain and mammary gland, among others. Tolfenamic acid anti-inflammatory used analgesic antipyretic humans animals. Recently, tolfenamic has been repurposed antitumoral for use chronic human diseases Alzheimer. aim this work was to study whether vitro Abcg2 substrate, investigate potential role plasma exposure, secretion into milk tissue accumulation drug. Using transepithelial assays with transduced Abcg2, we showed substrate Abcg2. vivo effect tested using wild-type Abcg2−/− mice, showing after oral intravenous administration acid, its area under concentration-time curve mice between 1.7 1.8-fold higher compared mice. also liver testis administration. In study, demonstrate transported by levels well distribution are affected pharmacological toxicological consequences.