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Dingemanse, J. et al.

Dingemanse, Meyerhoff, Schadrack,

Effect of the catechol-O-methyltransferase inhibitor entacapone on the steady-state pharmacokinetics and pharmacodynamics of 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.[1]

References

Effect of the catechol-O-methyltransferase inhibitor entacapone on the steady-state pharmacokinetics and pharmacodynamics of warfarin. Dingemanse, J., Meyerhoff, C., Schadrack, J. British journal of clinical pharmacology. (2002) [Pubmed]

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