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StudyDrug metabolism and disposition: the biological fate of chemicals · 2026

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

Mostafa Ben Ahmed, Anne M Filppula, Aleksi Tornio

Internal MedicineStudy

Modeling predicted 144 potential drug interactions with direct oral anticoagulants.

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

Mostafa Ben Ahmed … Aleksi Tornio

Drug metabolism and disposition: the biological fate of chemicals · 2026

Background

Direct oral anticoagulants (direct oral anticoagulants) are susceptible to drug-drug interactions involving both transport and metabolism.

Methods

In this study, we examined potential interactions of select precipitants with apixaban, dabigatran, edoxaban, and rivaroxaban using a 3-step static mechanistic combinatorial modeling approach.

Results

144

reveals 47 drugs that could raise or lower anticoagulant blood levels

More results

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.

More results

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).

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Conclusion

Using our validated model, we predicted 144 drug-drug interaction signals with potential clinical significance.

Post

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

Modeling predicted 144 potential drug interactions with direct oral anticoagulants.

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