Absolute Bioavailability of Esaxerenone and Food Effects on its Pharmacokinetics After a Single Oral Dose in Healthy Japanese Subjects: An Open-Label Crossover Study

INTRODUCTION: To investigate the absolute bioavailability of esaxerenone and the effects of food on its pharmacokinetics (PK) after a single oral dose in healthy Japanese subjects. METHODS: Twenty-four Japanese males aged 20–45 years were randomised to six groups (each n = 4) in this single-centre, open-label, three-way, three-period crossover study. Esaxerenone (5 mg) was administered in the fasting state as a single oral dose, single intravenous infusion over 1 h, or in the postprandial state as a single oral dose. Plasma samples were taken before and during the 96 h after drug administration. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry. PK parameters were calculated using noncompartmental analysis, and safety was assessed. RESULTS: After fasting intravenous administration, total body clearance was 3.69 L h(−1) and volume of distribution was 92.7 L. The plasma concentration–time profile of esaxerenone was similar after fasting and postprandial administration. Absolute bioavailability of a single oral 5-mg dose of esaxerenone was 89.0% in the fasting state and 90.8% postprandially. Point estimates (1.010 and 1.019, respectively) and 90% confidence intervals for geometric least squares mean peak plasma concentrations and area under the plasma concentration–time curve ratios after postprandial versus fasting oral esaxerenone were within the prespecified range (0.80, 1.25). No severe adverse events occurred throughout the study. CONCLUSIONS: Esaxerenone has a high absolute bioavailability of approximately 90% and food has no effect on esaxerenone PK after a single oral dose of 5 mg in healthy Japanese subjects. Additionally, no safety concerns were identified. CLINICAL TRIAL REGISTRATION: JapicCTI No. 163452. FUNDING: Daiichi Sankyo Co., Ltd.