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Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects
Author(s) -
Dieterle Walter,
Corynen Sophie,
Mann Jessica
Publication year - 2004
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2004.02160.x
Subject(s) - aliskiren , pharmacokinetics , pharmacodynamics , warfarin , medicine , prothrombin time , pharmacology , crossover study , renin inhibitor , partial thromboplastin time , bioequivalence , placebo , renin–angiotensin system , coagulation , atrial fibrillation , blood pressure , pathology , alternative medicine
Aims 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 C max 0.89 (0.82, 0.96) and 0.88 (0.80, 0.97), AUC(0,∞) 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.