Pharmacokinetic interactions of esaxerenone with amlodipine and digoxin in healthy Japanese subjects.
BMC Pharmacol Toxicol
; 21(1): 55, 2020 07 29.
Article
en En
| MEDLINE
| ID: mdl-32727577
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 (Cmax) and time to Cmax 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 Cmax, 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 Cmax, 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).Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Pirroles
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Sulfonas
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Bloqueadores de los Canales de Calcio
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Amlodipino
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Digoxina
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Antagonistas de Receptores de Mineralocorticoides
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Antihipertensivos
Tipo de estudio:
Clinical_trials
Límite:
Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
BMC Pharmacol Toxicol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón