Pharmacokinetic and dynamic interactions of the angiotensin-converting enzyme inhibitor imidapril with hydrochlorothiazide, bisoprolol and nilvadipine.
Eur J Clin Pharmacol
; 57(4): 275-84, 2001 Jul.
Article
em En
| MEDLINE
| ID: mdl-11549204
ABSTRACT
OBJECTIVE:
The pharmacokinetic and dynamic interactions of the angiotensin-converting enzyme (ACE) inhibitor imidapril with other therapeutic principles used in hypertension and heart failure were evaluated.METHODS:
In three separate, double-blind, placebo-controlled, four-way cross-over studies in healthy volunteers (n = 16 each), single oral doses of imidapril 10 mg (I), hydrochlorothiazide 12.5 mg (H), bisoprolol 5 mg (B) and nilvadipine 8 mg (N) were administered as monotherapies, and in IH, IB and IN combinations. Plasma concentrations of imidaprilat and H were followed up to 48 h, those of B and N up to 24 h and area under the concentration time curve (AUC), maximum plasma concentration (Cmax) and time to Cmax (tmax) were determined. Blood pressure (BP), heart rate (HR) and non-invasive haemodynamics [total peripheral resistance (TPR, N and H), systolic time intervals (STI, N and H), and plasma renin activity (PRA)] were assessed up to 24 h.RESULTS:
There were no pharmacokinetic interactions between I plus H, B or N. Bioequivalence between single and combined administrations was verified for all investigational compounds [AUC point estimates (90% confidence interval CI) imidaprilat IH 109% (97.8, 122.8); IB 99.6% (91.2, 109.4); IN 105.7% (92.1, 121.3); H 96.6% (92.5, 100.8); B 103% (100.2, 105.8); N 98% (89, 108)]. The haemodynamic effects were mostly additive and without relevant pharmacodynamic interactions. I significantly reduced the BP by 5-8 mmHg, B by 4-8 mmHg and N by 4-6 mmHg. In addition, H induced a significant reduction of the preload as seen from STI, and B significantly reduced HR (-5 bpm). N induced a significant decrease in TPR (about 15% of baseline values) and showed corresponding changes in STI. PRA increased significantly following I alone (1.5-2.0 ng/ml/h), as well as combined with N (2.5 ng/ ml/h) or H (3.1 ng/ml/h). This increase was clearly blunted by the co-administration of B (0.6 ng/ml/h).CONCLUSIONS:
The combination of imidapril with a diuretic, beta-adrenoceptor antagonist or calcium-channel blocker seems a reasonable and safe treatment option when striving for additive pharmacodynamic effects not accompanied by relevant pharmacokinetic interactions.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Enzima Conversora de Angiotensina
/
Bloqueadores dos Canais de Cálcio
/
Nifedipino
/
Bisoprolol
/
Antagonistas Adrenérgicos beta
/
Imidazolidinas
/
Inibidores de Simportadores de Cloreto de Sódio
/
Hidroclorotiazida
/
Imidazóis
/
Anti-Hipertensivos
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Clin Pharmacol
Ano de publicação:
2001
Tipo de documento:
Article