• entacapone;
  • interaction;
  • Parkinson's disease;
  • pharmacodynamics;
  • pharmacokinetics;
  • warfarin

Aims  To investigate the influence of a multiple-dose regimen with the catechol-O-methyltransferase inhibitor entacapone on the pharmacokinetics and pharmacodynamics of warfarin.

Methods  In a randomized, double-blind, two-way cross-over study, 12 healthy subjects (gender ratio 1 : 1) received treatment for 1 week with either entacapone 200 mg four times daily or placebo during individually optimized treatment with warfarin (INR 1.4–1.8). The effect of entacapone on the steady-state pharmacokinetics of both R- and S-warfarin was determined and, in addition, INR values were measured. The key pharmacokinetic variables were AUCss, Cmax and tmax.

Results  Entacapone increased the exposure to R-warfarin by 18% (90% CI: 111, 126%), and caused a 13% (6, 19%) increase in INR values. No effect was seen on the pharmacokinetics of the pharmacologically more potent S-enantiomer. Safety and tolerability variables did not show any difference between the treatment phases.

Conclusions  In healthy subjects, entacapone displays a slight pharmacokinetic interaction with R-warfarin but, based on the lack of a clinically relevant pharmacodynamic interaction, it appears that it can also be used safely in Parkinson's disease patients who are receiving warfarin.