title: The stereoselective effects of bucolome on the pharmacokinetics and pharmacodynamics of racemic warfarin.
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.
authors: Department of Molecular Pathophysiology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
authors: K
authors: K
authors: Matsumoto
authors: S
authors: S
authors: Ishida
authors: K
authors: K
authors: Ueno
authors: H
authors: H
authors: Hashimoto
authors: M
authors: M
authors: Takada
authors: K
authors: K
authors: Tanaka
authors: S
authors: S
authors: Kamakura
authors: K
authors: K
authors: Miyatake
authors: M
authors: M
authors: Shibakawa
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000925:Anticoagulants / Q000493:pharmacokinetics*; D001463:Barbiturates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006331:Heart Diseases / Q000188:drug therapy; D006801:Humans; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013237:Stereoisomerism; D013997:Time Factors; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D001463:Barbiturates; D014859:Warfarin; C084817:bucolome