Dataset Information

Pharmacokinetic interactions of esaxerenone with amlodipine and digoxin in healthy Japanese subjects.

ABSTRACT:

Background

To investigate the effects of coadministration of esaxerenone with amlodipine on the pharmacokinetics (PK) of each drug, and of esaxerenone on the PK of digoxin.

Methods

In three open-label, single-sequence, crossover studies, healthy Japanese males received single oral doses of esaxerenone 2.5 mg (Days 1, 15), with amlodipine 10 mg/day (Days 8-18) (Study 1, N = 24); single doses of amlodipine 2.5 mg (Days 1, 21), with esaxerenone 5 mg/day (Days 8-25) (Study 2; N = 20); or digoxin 0.25 mg/day (Days 1-15) with esaxerenone 5 mg/day (Days 11-15) (Study 3; N = 20). PK parameters and safety were assessed.

Results

Study 1: esaxerenone peak plasma concentration (C_max) and time to C_max were unaltered by amlodipine coadministration, but mean half-life was slightly prolonged from 18.5 to 20.9 h. Geometric least-squares mean (GLSM) ratios for C_max, area under the plasma concentration-time curve (AUC) from zero to last measurable concentration and from zero to infinity for esaxerenone + amlodipine versus esaxerenone were 0.958, 1.154, and 1.173, respectively. Study 2: corresponding GLSM ratios for amlodipine + esaxerenone versus amlodipine were 1.099, 1.185, and 1.214. Study 3: esaxerenone did not markedly alter digoxin PK. GLSM ratios for C_max, trough plasma concentration, and AUC during a dosing interval for digoxin versus esaxerenone + digoxin were 1.130, 1.088, and 1.072, respectively.

Conclusions

No drug-drug interactions are expected during combination therapy with esaxerenone and either amlodipine or digoxin, based on a lack of any clinically relevant PK changes.

Trial registration

Studies 1 and 2: JapicCTI-163379 (registered on 20 September 2016); Study 3: JapicCTI-163443 (registered on 24 November 2016).

SUBMITTER: Kirigaya Y

PROVIDER: S-EPMC7389645 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacokinetic interactions of esaxerenone with amlodipine and digoxin in healthy Japanese subjects.

Kirigaya Yoshiaki Y Shiramoto Masanari M Ishizuka Tomoko T Uchimaru Hinako H Irie Shin S Kato Manabu M Shimizu Takako T Nakatsu Takafumi T Nishikawa Yasuhiro Y Ishizuka Hitoshi H

BMC pharmacology & toxicology 20200729 1

<h4>Background</h4>To investigate the effects of coadministration of esaxerenone with amlodipine on the pharmacokinetics (PK) of each drug, and of esaxerenone on the PK of digoxin.<h4>Methods</h4>In three open-label, single-sequence, crossover studies, healthy Japanese males received single oral doses of esaxerenone 2.5 mg (Days 1, 15), with amlodipine 10 mg/day (Days 8-18) (Study 1, N = 24); single doses of amlodipine 2.5 mg (Days 1, 21), with esaxerenone 5 mg/day (Days 8-25) (Study 2; N = 20); ...[more]

PMID: 32727577

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Dataset Information

Pharmacokinetic interactions of esaxerenone with amlodipine and digoxin in healthy Japanese subjects.

Background

Methods

Results

Conclusions

Trial registration

Publications

Pharmacokinetic interactions of esaxerenone with amlodipine and digoxin in healthy Japanese subjects.

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