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- W1265119725 abstract "Coumadin (R/S-warfarin) anticoagulation therapy remains challenging due to a narrow therapeutic range and high inter-individual variations in response. We hypothesize that plasma metabolite profiles capture clinically relevant variations in warfarin metabolism as a resource to improve therapeutic strategies to minimize risk. We profiled R- and S-warfarin and ten oxidized metabolites from fifty-nine patient plasma samples using a novel LC-MS method. Profiles included R- and S-6-, 7-, and 4′-hydroxywarfarin plus four 10-hydroxywarfarin diastereomers, yet neither R- nor S-8-hydroxywarfarin was detected. Profiles differed significantly from those generated by R- and S-warfarin using human liver microsomes and thus indicate variations in secondary metabolism and/or transport contributing to metabolite levels and their impact on dose-responses. Multi-linear regression analysis of metabolite levels normalized to parent drugs identified the relative importance and factors influencing their contributions to R- and S-warfarin metabolism as evidence of the ability of metabolite profiles to capture the metabolic phenotype. These seminal findings provide a promising foundation to identify metabolite patterns as predictors of patient dose-response to warfarin during anticoagulant therapy. Work was supported by National Institutes of Health (5R25HL108825-02), National Institutes of Health and UAMS Translational Research Institute (UL1RR029884), and American Heart Association (13GRNT1690043)." @default.
- W1265119725 created "2016-06-24" @default.
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- W1265119725 date "2015-04-01" @default.
- W1265119725 modified "2023-09-23" @default.
- W1265119725 title "Warfarin Metabolite Profiles Reveal the Importance of Factors on Patient Dose‐Responses to Anticoagulant Therapy" @default.
- W1265119725 doi "https://doi.org/10.1096/fasebj.29.1_supplement.716.14" @default.
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