Pharmacodynamic evaluation of warfarin and rosuvastatin co-administration in healthy subjects.
OBJECTIVE
To determine whether co-administration of rosuvastatin alters the pharmacodynamics of warfarin, thereby requiring additional monitoring of the anticoagulant effects of warfarin.


METHODS
In this open-labeled, placebo-controlled, randomized, two-period, crossover trial with a washout period of 15 days, 12 healthy male volunteers were administered daily oral doses of 5 mg warfarin for 14 days. Either rosuvastatin 40 mg/day (treatment A) or placebo (treatment B) was concomitantly administered on days 8-14. The pharmacodynamic parameters prothrombin time (PT) and international normalized ratio (INR) were evaluated on all 14 days pre-dose during both study periods. On the 8th, 10th, 12th, and 14th days of each study period, PT and INR were also measured at 4 h post-dose of rosuvastatin or placebo. Bleeding time and clotting time were assessed on the 1st, 8th, and 14th days pre-dose.


RESULTS
Data of 10 subjects have been analyzed. No significant effect of rosuvastatin was seen on the steady-state pharmacodynamics of warfarin during concomitant administration.


CONCLUSIONS
Rosuvastatin did not significantly alter the anticoagulant effects of warfarin in this study.
Jindal
Daisy
D
Apollo Hospital, New Delhi, India. jindal_daisy@yahoo.com
Tandon
Monika
M
Sharma
Sanjay
S
Pillai
K K
KK
D000284:Administration, Oral; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001777:Blood Coagulation / Q000187:drug effects; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005464:Fluorobenzenes / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D019934:International Normalized Ratio; D008297:Male; D011517:Prothrombin Time; D011743:Pyrimidines / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000925:Anticoagulants; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D014859:Warfarin; D000068718:Rosuvastatin Calcium