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 mgrifampicin 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.
RCT Entities:
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.
Authors: Er-jia Wang; Karen Lew; Christopher N Casciano; Robert P Clement; William W Johnson Journal: Antimicrob Agents Chemother Date: 2002-01 Impact factor: 5.191
Authors: Lauri I Kajosaari; Mikko Niemi; Mikko Neuvonen; Jouko Laitila; Pertti J Neuvonen; Janne T Backman Journal: Clin Pharmacol Ther Date: 2005-10 Impact factor: 6.875
Authors: Sujata Vaidyanathan; Gian Camenisch; Helmut Schuetz; Christine Reynolds; Ching-Ming Yeh; Marie-Noelle Bizot; Hans Armin Dieterich; Dan Howard; William P Dole Journal: J Clin Pharmacol Date: 2008-09-10 Impact factor: 3.126
Authors: Byung-Hee Oh; Jerry Mitchell; James R Herron; Jenny Chung; Mahmudul Khan; Deborah L Keefe Journal: J Am Coll Cardiol Date: 2007-03-20 Impact factor: 24.094
Authors: Sebastian Härtter; Michael Koenen-Bergmann; Ashish Sharma; Gerhard Nehmiz; Ute Lemke; Wolfgang Timmer; Paul A Reilly Journal: Br J Clin Pharmacol Date: 2012-09 Impact factor: 4.335
Authors: Mathieu S Bolhuis; Prashant N Panday; Arianna D Pranger; Jos G W Kosterink; Jan-Willem C Alffenaar Journal: Pharmaceutics Date: 2011-11-18 Impact factor: 6.321