Intestinal permeability and P-glycoprotein-mediated efflux transport of ticagrelor in Caco-2 monolayer cells.
Ticagrelor is the unique reversible oral antiplatelet drug commercialized today. During this study, the intestinal permeability of ticagrelor and its potential P-glycoprotein (P-gp)-mediated active transport were assessed. To this end, bidirectional transport of ticagrelor was performed across Caco-2 (human epithelial colorectal adenocarcinoma) monolayer model in the presence and absence of potent P-gp inhibitor valspodar. Ticagrelor presented an apical-basolateral apparent permeability coefficient (Papp ) of 6.0 × 10-6 cm/s. On the other hand, mean efflux ratio (ER) of 2.71 was observed for ticagrelor describing a higher efflux permeability compared to the influx component. Valspodar showed a significant inhibitory effect on the efflux of ticagrelor suggesting involvement of P-gp in its oral disposition. Co-incubation of the P-gp inhibitor decreased the efflux Papp of ticagrelor from 1.60 × 10-5 to 1.13 × 10-5 cm/s and decreased its ER by 70%. Results suggest a modest active transport of ticagrelor by P-gp across the Caco-2 cell monolayer. The co-administration of ticagrelor with a P-gp inhibitor seems altogether unlikely to have an extended impact on pharmacokinetics of ticagrelor and cause bleeding events in patients.
['Marsousi|Niloufar|N|', 'Doffey-Lazeyras|Fabienne|F|', 'Rudaz|Serge|S|', 'Desmeules|Jules A|JA|', 'Daali|Youssef|Y|']
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 D000241:Adenosine D001693:Biological Transport, Active D018938:Caco-2 Cells D045744:Cell Line, Tumor D003524:Cyclosporins D006801:Humans D007413:Intestinal Mucosa D010539:Permeability D021381:Protein Transport D000077486:Ticagrelor
intestinal permeability transport ticagrelor P-glycoprotein Caco-2 cell absorption