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Effect of Rosuvastatin on Warfarin Pharmacodynamics and Pharmacokinetics
Author(s) -
Simonson Steven G.,
Martin Paul D.,
Mitchell Patrick D.,
Lasseter Kenneth,
Gibson Gordon,
Schneck Dennis W.
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005278224
Subject(s) - pharmacodynamics , rosuvastatin , pharmacokinetics , warfarin , pharmacology , medicine , atrial fibrillation
The effect of rosuvastatin on warfarin pharmacodynamics and pharmacokinetics was assessed in 2 trials. In trial A (a randomized, double‐blind, 2‐period crossover study), 18 healthy volunteers were given rosuvastatin 40 mg or placebo on demand (o.d.) for 10 days with 1 dose of warfarin 25 mg on day 7. In trial B (an open‐label, 2‐period study), 7 patients receiving warfarin therapy with stable international normalized ratio values between 2 and 3 were coadministered rosuvastatin 10 mg o.d. for up to 14 days, which increased to rosuvastatin 80 mg if the international normalized ratio values were <3 at the end of this period. The results indicated that rosuvastatin can enhance the anticoagulant effect of warfarin. The mechanism of this drug‐drug interaction is unknown. Rosuvastatin had no effect on the total plasma concentrations of the warfarin enantiomers, but the free plasma fractions of the enantiomers were not measured. Appropriate monitoring of the international normalized ratio is indicated when this drug combination is coadministered.