In vitro Bioaccessibility, Bioavailability, and Plasma Protein Interaction of New Oral Anticoagulants in the Presence of Macronutrients.

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.