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Effect of Moricizine on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Volunteers
Author(s) -
Benedek Irma H.,
King ShangYing P.,
Powell Richard J.,
Agra Allison M.,
Schary William L.,
Pieniaszek Henry J.
Publication year - 1992
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127009203200612
Subject(s) - pharmacokinetics , warfarin sodium , pharmacodynamics , pharmacology , prothrombin time , warfarin , volume of distribution , oral administration , elimination rate constant , drug interaction , medicine , chemistry , anticoagulant , atrial fibrillation
Moricizine HCl, a new orally active antiarrhythmic agent, induces its own hepatic metabolism and consequently may interfere with the metabolism of warfarin, a drug used commonly by cardiac patients that also is subject to extensive hepatic metabolism. Both drugs are also highly protein bound in plasma. To assess the possibility of an interaction, single‐dose sodium warfarin (25 mg oral Coumadin, Du Pont Pharmaceuticals, Wilmington, DE) pharmacokinetics, pharmacodynamics, and plasma protein binding were examined in 12 healthy mate volunteers 14 days before and 14 days after starting chronic oral moricizine HCl administration (250 mg every 8 hours). The terminal elimination rate constant of warfarin was increased by about 10% when measured in the presence of chronic moricizine administration. However, oral plasma clearance, apparent volume of distribution, maximum peak plasma concentration, time to reach peak concentration, and protein binding were unaffected. More importantly, there was no evidence of a pharmacodynamic interaction based on the prothrombin time profile. It was concluded that no clinically significant interaction occurs under these conditions.