Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects.
OBJECTIVE
To investigate the effects of aliskiren, an oral renin inhibitor, on the pharmacokinetics and pharmacodynamics of warfarin.


METHODS
In a single-blind, placebo-controlled, randomized, two-period crossover study, 15 healthy male and female subjects received a single oral dose of 25 mg racemic warfarin twice, once in the morning of the 8th day of treatment with 150 mg aliskiren and once at the same time point during treatment with placebo. Blood samples were collected for the measurement of prothrombin time (PT) and activated thromboplastin time (aPTT) and for determination of plasma concentrations of (R)- and (S)-warfarin.


RESULTS
Aliskiren treatment had no effect on the blood coagulation parameters (PT, INR and aPTT). The ratios of least square means (90% CI) of pharmacokinetic parameters in the presence and absence of aliskiren for (R)- and (S)-warfarin were Cmax 0.89 (0.82, 0.96) and 0.88 (0.80, 0.97), AUC(0, infinity) 1.00 (0.94, 1.07) and 1.06 (0.96, 1.16) and t(1/2) 0.99 (0.92, 1.07) and 1.05 (0.96, 1.14).


CONCLUSIONS
Multiple doses of aliskiren had no detectable effect on the pharmacokinetics or pharmacodynamics of a single dose of warfarin in healthy subjects.
Dieterle
Walter
W
Drug Disposition Consultants, Loerrach, Germany.
Corynen
Sophie
S
Mann
Jessica
J
D000328:Adult; D000577:Amides; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018592:Cross-Over Studies; D005260:Female; D005650:Fumarates / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D016037:Single-Blind Method; D014859:Warfarin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000092502:Renin Inhibitors
D000577:Amides; D000925:Anticoagulants; D005650:Fumarates; D014859:Warfarin; D000092502:Renin Inhibitors; C446481:aliskiren