Effect of Multiple-Dose Diltiazem on the Pharmacokinetics of the Renin Inhibitor ACT-077825.
Clin Pharmacol Drug Dev
; 2(2): 113-9, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-27121666
ABSTRACT
This open-label, randomized study evaluated the effects of steady-state diltiazem on the pharmacokinetic, safety, and tolerability profile of a single dose of the novel renin inhibitor ACT-077825. Twelve healthy Caucasian male subjects (20-50 years) received in treatment sequence A, a single dose of 100 mg ACT-077825 (Days 1 and 17), and oral diltiazem 300 mg once daily (Days 14-26). In treatment sequence B, subjects received a single dose of 100 mg ACT-077825 (Days 4 and 22) and oral diltiazem 300 mg once daily (Days 1-13). ACT-077825 alone and combined with diltiazem was generally well tolerated. On average, the systemic exposure to ACT-077825 was higher in the presence of diltiazem. For AUC0-∞ and t1/2 , the upper limit of the 90% confidence interval (CI) of the geometric mean ratios was outside the study-specific 0.5-2.0 equivalence boundaries, that is, 1.92 (90% CI 1.30, 2.83) and 1.58 (90% CI 1.22, 2.04), respectively. In conclusion, diltiazem markedly affected the pharmacokinetics of ACT-077825, probably via inhibition of CYP3A4 activity, without changing its safety and tolerability profile in healthy male subjects. Whether such an interaction will require for therapeutic dose adjustment of ACT-077825 co-administered with diltiazem has to be assessed once the dose-response relationship of ACT-077825 in hypertensive patients is determined.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Clinical_trials
Idioma:
En
Revista:
Clin Pharmacol Drug Dev
Año:
2013
Tipo del documento:
Article
País de afiliación:
Suiza