Bioavailability of dronedarone tablets administered with or without food in healthy participants

Abstract

Study objective

There is inadequate awareness of the effect of food on the bioavailability of dronedarone. We report results from two phase 1 studies assessing the effect of food on dronedarone's bioavailability.

Design, setting and participants

Study 1; single-center, open-label, randomized study in healthy adults (males and females). Study 2; single-center, open-label, randomized study in healthy males.

Interventions

Study 1; a single 400-mg oral dose of dronedarone (marketed formulation) in fed (high-fat [47.4 g] meal) and fasted states. Study 2; a single 800-mg oral dose of dronedarone (two 400-mg tablets) after fat-rich (37.3 g) and low-fat (5.3 g) meals, and after fasting.

Main outcome measures

Pharmacokinetic parameters including maximum plasma concentration (C_max) and area under the curve from time 0 to last measurable time (AUC_last) were assessed for dronedarone and its active N-debutyl metabolite.

Results

Twenty-six participants were included in Study 1 and nine in Study 2. In Study 1, administration of 400 mg dronedarone with a high-fat meal vs. fasted state resulted in 2.8-fold and 2.0-fold increases in C_max and AUC_last, respectively. In Study 2, administration of 800 mg dronedarone with a fat-rich or low-fat meal vs. fasted state resulted in 4.6-fold and 3.2-fold increases in C_max, respectively, and 3.1-fold and 2.3-fold increases, respectively, in AUC_last. Results for the N-debutyl metabolite were similar to dronedarone. No adverse events were considered related to dronedarone.

Conclusion

With food, the bioavailability of dronedarone is markedly increased. In clinical practice, dronedarone should be administered with a complete meal to maximize drug absorption.