Effect of Cilostazol on the Pharmacokinetics and Pharmacodynamics of Warfarin

Abstract

Objective

To evaluate the effect of cilostazol administration on warfarin pharmacokinetics and pharmacodynamics following a single 25mg dose of warfarin.

Design

A randomised double-blind 2-period crossover with healthy volunteers receiving either 100mg cilostazol twice daily for 13 days or matching placebo twice daily for 13 days, and the other treatment 21 days later. A single 25mg dose of warfarin was given 14 days prior to the start of the study, and 7 days after the cilostazol and placebo treatments.

Study Participants

15 normal healthy male volunteers.

Outcome Measures

Noncompartmental pharmacokinetic parameters for (R)-and (S)-warfarin, the area under the curve of the prothrombin time (AUCPT), activated partial thromboplastin time (AUCaPTT), Ivy bleeding times, unbound fraction (f_u) of cilostazol, and warfarin were determined for each individual.

Results

For (R)- and (S)-warfarin, the 90% confidence intervals for the ratios of the geometric means (90% CI) of the maximum plasma concentration and area under the plasma concentration-time curve were between 0.88 to 1.03. The 90% CI for the AUCPT and AUCaPTT was between 0.95 and 1.06. For Ivy bleeding time, the 90% CI for the ratios of the geometric means ranged between 0.71 and 1.22. The f_u of cilostazol did not differ significantly between the 2 treatments. There was a 17% increase in the f_u of warfarin (p < 0.05), which was not clinically significant.

Conclusions

Coadministration of warfarin with twice daily administration of cilostazol 100mg did not alter (R)- and (S)-warfarin pharmacokinetics, prothrombin time, partial thromboplastin time, Ivy bleeding times, or cilostazol protein binding.