Rifampicin reduces the plasma concentrations and the renin-inhibiting effect of aliskiren.
OBJECTIVE
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.
Tapaninen
Tuija
T
Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.
Neuvonen
Pertti J
PJ
Niemi
Mikko
M
D000328:Adult; D000577:Amides / Q000097:blood* / Q000494:pharmacology* / Q000652:urine; D000959:Antihypertensive Agents / Q000097:blood* / Q000494:pharmacology* / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D005260:Female; D005650:Fumarates / Q000097:blood* / Q000494:pharmacology* / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D012083:Renin / Q000097:blood; D012293:Rifampin / Q000009:adverse effects*; D000092502:Renin Inhibitors
D000577:Amides; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D005650:Fumarates; D012083:Renin; D012293:Rifampin; D000092502:Renin Inhibitors; C446481:aliskiren