Rifampicin reduces the plasma concentrations and the renin-inhibiting effect of aliskiren

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.