A 3-step static mechanistic modeling approach to predicting transporter- and enzyme-mediated interaction signals of direct oral anticoagulants.

In this approach, we (1) calculated apparent estimates of the fractions of efflux transport (f e ) of the 4 direct oral anticoagulants by the intestinal breast cancer resistance protein and intestinal permeability glycoprotein (P-gp), (2) validated our estimates, and (3) used them to simulate unstudied drug interactions with the anticoagulants.

We estimated P-gp and breast cancer resistance protein transport to play a similar role in the interactions of apixaban and rivaroxaban (f e_P-gp = 0.21, f e_breast cancer resistance protein = 0.13).