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Concomitant etodolac affects neither the unbound clearance nor the pharmacologie effect of warfarin
Author(s) -
Ermer James C,
Hicks David R,
Wheeler Sarah C,
Kraml Michael,
Jusko William J
Publication year - 1994
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1994.31
Subject(s) - etodolac , warfarin , concomitant , pharmacology , pharmacokinetics , prothrombin time , drug interaction , crossover study , chemistry , clinical pharmacology , volume of distribution , medicine , anesthesia , placebo , atrial fibrillation , alternative medicine , pathology
Potential interactions between the nonsteroidal anti‐inflammatory etodolac and the anticoagulant warfarin were studied in 18 healthy subjects by use of a randomized, three‐period crossover design. Each treatment lasted 2½ days and consisted of warfarin, etodolac, or both drugs. Prothrombin time was determined daily during each warfarin period to measure pharmacologic effect. Total serum concentration and unbound fraction of both drugs were determined over the dose interval after the last dose of the study drug(s). Concomitant etodolac did not affect the prothrombin time response or the unbound clearance of warfarin. During concomitant etodolac administration, the median peak concentration of total warfarin was significantly decreased by 19% ( p = 0.005), median total clearance was significantly increased by 13% ( p = 0.0123), and the unbound fraction tended to increase (median unbound fraction of warfarin, 1.245% with etodolac and 1.045% without etodolac; p = 0.0979; not statistically significant). These observations suggest a small displacement of warfarin from serum protein by etodolac or a metabolite of etodolac. No etodolac pharmacokinetic parameter was significantly affected by concomitant warfarin administration. Thus etodolac does not appear to alter the unbound clearance of warfarin or augment its pharmacologic effect. Nevertheless, it is prudent that clinical monitoring be done for individuals taking these two compounds concomitantly. Clinical Pharmacology and Therapeutics (1994) 55, 305–316; doi: 10.1038/clpt.1994.31