Abstract |
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.
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Authors | K Matsumoto, S Ishida, K Ueno, H Hashimoto, M Takada, K Tanaka, S Kamakura, K Miyatake, M Shibakawa |
Journal | Journal of clinical pharmacology
(J Clin Pharmacol)
Vol. 41
Issue 4
Pg. 459-64
(Apr 2001)
ISSN: 0091-2700 [Print] England |
PMID | 11304904
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Anticoagulants
- Barbiturates
- Warfarin
- bucolome
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Topics |
- Administration, Oral
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Anti-Inflammatory Agents, Non-Steroidal
(therapeutic use)
- Anticoagulants
(pharmacokinetics)
- Barbiturates
(administration & dosage, pharmacology, therapeutic use)
- Dose-Response Relationship, Drug
- Drug Interactions
- Female
- Heart Diseases
(drug therapy)
- Humans
- Japan
- Male
- Metabolic Clearance Rate
- Middle Aged
- Stereoisomerism
- Time Factors
- Warfarin
(administration & dosage, pharmacokinetics, pharmacology)
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