Abstract
Warfarin is an anticoagulant used for the prevention of thrombosis and embolism. Hydroxylation of warfarin via CYP450s is well documented; however, its biotransformation by UGTs has not been investigated. The activities of 8 human recombinant UGTs, towards warfarin and its hydroxylated metabolites have been assessed with R-warfarin and racemic warfarin, 4′-OH-, 6-OH-, 7-OH-, and 10-OH-warfarin. HPLC-UV-Vis assays and HPLC-MS/MS product confirmations established that UGT1A10, −1A1, −1A3, and −1A8 (highest to lowest activity) conjugated 7-OH-warfarin. Kinetic assays measured Km and Vmax values for 7-OH-warfarin glucuronidation at 165.5 ± 42.7 μM and 1.14 ± 0.1 nmol/mg protein/min, respectively by UGT1A10. 6-OH-warfarin is glucuronidated by 1A1 and 1A10, and 4′-OH-warfarin is glucuronidated by 1A10, but at low levels. Warfarin, 10-OH-warfarin, or R-warfarin were not glucuronidated. This is the first demonstration that major CYP450 metabolites of warfarin are glucuronidated by human recombinant UGTs, with UGT1A10 being the major isoform involved in human phase II biotransformation. (NIH-DK60109 to AR-P; Bioterrorism Cooperative Agreement U90/CCU616974-07 and APHL-Fellowship to JHM)
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
