Effect of the catechol-O-methyltransferase inhibitor entacapone on the steady-state pharmacokinetics and pharmacodynamics of warfarin
Article first published online: 2 MAY 2002
British Journal of Clinical Pharmacology
Volume 53, Issue 5, pages 485–491, May 2002
How to Cite
Dingemanse, J., Meyerhoff, C. and Schadrack, J. (2002), Effect of the catechol-O-methyltransferase inhibitor entacapone on the steady-state pharmacokinetics and pharmacodynamics of warfarin. British Journal of Clinical Pharmacology, 53: 485–491. doi: 10.1046/j.1365-2125.2002.01587.x
- Issue published online: 2 MAY 2002
- Article first published online: 2 MAY 2002
- Received 9 August 2001,accepted 20 December 2001.
- Parkinson's disease;
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.