Rifampicin reduces the plasma concentrations and the renin-inhibiting effect of aliskiren.
Eur J Clin Pharmacol
; 66(5): 497-502, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20179914
ABSTRACT
PURPOSE:
This study aimed to investigate the effect of rifampicin, an inducer of CYP3A4 and P-glycoprotein, on the pharmacokinetics and pharmacodynamics of aliskiren, a renin inhibitor used in the treatment of hypertension.METHODS:
In a randomized crossover study, 12 healthy volunteers took 600 mg rifampicin or placebo once daily for 5 days. On day 6, they ingested a single 150-mg dose of aliskiren. Plasma aliskiren concentrations were measured up to 72 h and urine concentrations up to 12 h; pharmacodynamic variables were measured up to 24 h.RESULTS:
Rifampicin reduced the peak plasma aliskiren concentration (C(max)) by 39% (95% confidence interval 0.41, 0.90; P = 0.017) and the area under the plasma aliskiren concentration-time curve AUC(0-infinity) by 56% (95% confidence interval 0.35, 0.56; P < 0.001). Rifampicin had no significant effect on aliskiren elimination half-life (t(1/2)) or its renal clearance (Cl(renal)). Plasma renin activity 24 h after aliskiren intake was 61% higher during the rifampicin phase than during the placebo phase (P = 0.008).CONCLUSIONS:
Rifampicin considerably reduces the plasma concentrations and the renin-inhibiting effect of aliskiren by decreasing its oral bioavailability.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Rifampina
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Renina
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Inibidores Enzimáticos
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Fumaratos
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Amidas
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Anti-Hipertensivos
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article