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Effect of the catechol‐ O ‐methyltransferase inhibitor entacapone on the steady‐state pharmacokinetics and pharmacodynamics of warfarin
Author(s) -
Dingemanse Jasper,
Meyerhoff Carsten,
Schadrack Jan
Publication year - 2002
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2002.01587.x
Subject(s) - entacapone , pharmacokinetics , warfarin , pharmacodynamics , pharmacology , catechol o methyl transferase , medicine , drug interaction , crossover study , placebo , tolerability , levodopa , chemistry , adverse effect , parkinson's disease , allele , biochemistry , alternative medicine , disease , pathology , gene , atrial fibrillation
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 AUC ss , C max and t max . 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.