Hydroxywarfarin

Brodifacoum [56073-10-0] is a substituted 4-hydroxywarfarin with a strikingly prolonged half-life in the human body (50,51). Although used as a rodenticide, it has been ingested by some humans and observed to persist from 50 days to eight months. Its use in humans may be prohibitive because of the excessively prolonged half-life in the body. 

Wienkers LC, Wurden CJ, Storch E, et al. Formation of (R)-8-hydroxywarfarin in human liver - microsomes - a new metabolic marker for the (S)-mephenytoin hydroxylase, P4502C19. Drug Metab Dispos 1996 24 610-614. 

Ngui JS, Chen Q, Shou M, et al. In vitro stimulation of warfarin metabolism by quinidine increases in the formation of 4 - and 10-hydroxywarfarin. Drug Metab Dispos 2001 29 877-886. 

Disposition in the Body. Readily absorbed after oral administration. The (R)-enantiomer of warfarin is metabolised mainly by reduction to (R5)-3 -hydroxywarfarin although 6-hydroxylation also occurs. The (5 )-enantiomer is metabolised mainly by 6- and... 

Wilson et al. [1989] used rank annihilation on MS/MS spectra of samples containing warfarin, different hydroxywarfarins, and phenylbutazone. The rank annihilation was... 

Lang, D. and R. Bocker (1995). Highly sensitive and speeific high-performanee liquid chromatographic analysis of 7-hydroxywarfarin, a marker for human cytochrome P-4502C9 activity. J. Chromatogr. Biomed. Appl. 672, 305—309. 

In general, despite lower free fraetion, S-warfarin is more rapidly eliminated than its antipode in humans, and hepatic metabolism acconnts for almost all of the elimination of the drug [60]. Warfarin is metabolized to 6-hydroxywarfarin, 7-hydroxywarfarin, and two rednced derivatives, the diastereomers of warfarin alcohol [60]. The metabolism of R-warfarin involves oxidation to 6-hydroxywarfarin and subseqnent reduction to (R,S)-warfarin alcohol. In contrast, S-warfarin is oxidized to 7-hydroxywarfarin and reduced to (S,S)-warfarin alcohol. The metabolic profiles of warfarin enantiomers in blood and urine were similar [53,60]. The ring-hydroxylated metabolites are inactive, and the activity of warfarin alcohols are snb-stantially less than the parent molecule [53,60]. S-warfarin may also be metabolized to 6-hydroxywarfarin [60]. 

Jones DR, Kim SY, Guderyon M, Yun CH, Moran JH, Miller GP (2010) Hydroxywarfarin metabolites potently inhibit CYP2C9 metabolism of 5-warfarin. Chem Res Toxicol 23 939-945... 

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