Background: Over the last years, a new generation of oral anticoagulants (NOACs), including
apixaban, rivaroxaban and dabigatran, has been developed for the control of thrombosis and related
disorders. The presence of food within the gastrointestinal (GI) tract can potentially affect the oral
bioavailability of drugs.
Objective: In the present paper, we evaluated the stability of these drugs in in vitro GI digestion, with
and without the main macronutrients such as proteins, lipids, carbohydrates, and fibers, and their ability
to enter into the systemic circulation. In addition, we examined the percentage of the drug binding
to plasma proteins, such as human serum albumin, high density- and low density lipoproteins.
Methods: The NOACs bioaccessibility was evaluated by an in vitro procedure simulating the gastrointestinal
enzymatic system, while their bioavailability was studied by cell culture of Caco-2 cells and in
vitro study of transepithelial transport. The in vitro transepithelial permeated NOACs were added to
plasma protein solutions simulating the average fasting plasma protein concentrations. The NOACs detection
was carried out by HPLC-DAD/ESI-MS analysis.
Results: GI digestion significantly reduces intestinal bioaccessibility and bioavailability of NOACs,
especially as regards apixaban and dabigatran. Interestingly, the co-digestion of fibers led to a strong
decrease of NOAC intestinal bioaccessibility and bioavailability, while the effects of the other macronutrients,
as well as a low fiber standard meal, had no significant influence in this sense.
Conclusion: Dabigatran, rivaroxaban and apixaban may be administered independently of a standard
meal, provided that it does not include a high amount of dietary fibers.