Inhibitory Effects of 17-α-Ethinyl-Estradiol and 17-β-Estradiol on Transport Via the Intestinal Proton-Coupled Amino Acid Transporter (PAT1) Investigated In Vitro and In Vivo

The proton-coupled amino acid transporter, PAT1, is known to be responsible for intestinal absorption drug substances such as gaboxadol and vigabatrin. aim of the present study was investigate, if 17-α-ethinyl-estradiol (E-E2) 17-β-estradiol (E) inhibit PAT1-mediated proline taurine in vitro Caco-2 cells vivo using Sprague-Dawley rats assess potential taurine-drug interactions. E E-E2 inhibited uptake with IC50 values 10.0–50.0 μM without major effect on other solute carriers transporter (TauT), di/tri-peptide (PEPT1), serotonin (SERT1). In PAT1-expressing oocytes were non-translocated inhibitors. cells, lowered maximal capacity PAT1 a non-competitive manner. Likewise, transepithelial permeability reduced presence E-E2. male Sprague Dawley pre-dosed decreased plasma concentration (Cmax) increased time (tmax) reach this indicated, suggesting possibility an substrates. conclusion, identified inhibitors PAT1.