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The Stereoselective Effects of Bucolome on the Pharmacokinetics and Pharmacodynamics of Racemic Warfarin
Author(s) -
Matsumoto Kana,
Ishida Shigenobu,
Ueno Kazuyuki,
Hashimoto Hiroshi,
Takada Mitsutaka,
Tanaka Kazuhiko,
Kamakura Shiro,
Miyatake Kunio,
Shibakawa Masahiko
Publication year - 2001
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 - 10.1177/00912700122010186
Subject(s) - warfarin , pharmacodynamics , pharmacokinetics , pharmacology , anticoagulant , medicine , drug interaction , atrial fibrillation
The objective of this study was to investigate the stereoselective influence of bucolome on the pharmacokinetics and pharmacodynamics of warfarin in Japanese inpatients with heart disease. Thirty patients were administered a fixed‐maintenance dose of warfarin alone once a day for at least 7 days. The other 25 patients were concomitantly administered warfarin and a 300 mg dose of bucolome once a day, and blood samples were collected on days 1, 4, 7, 14, or 21 after administration of bucolome. Serum concentration of warfarin enantiomers was measured by a chiral reversed‐phase HPLC‐ultraviolet detection method. The PT‐INR was used as a measure of the pharmacodynamic effect of warfarin. Coadministration of bucolome and warfarin had no effect on serum (R)‐warfarin concentration and significantly increased serum (S)‐warfarin concentration compared with warfarin alone. The PT‐INR of warfarin alone was significantly lower with bucolome cotreatment. These results indicate that the augmented anticoagulant effect of warfarin by bucolome is due to inhibition of (S)‐warfarin metabolism in vivo. When bucolome is added to a stabilized regimen of warfarin therapy, the dose of warfarin should be reduced by about 30% to 60%, and caution should be exercised during the first 7 days after coadministration of bucolome.