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- W1994237400 abstract "The pharmacokinetics and urinary metabolic profile of R and S-warfarin, following administration of a 1.5 mg/kg oral dose of racemic warfarin, alone and 4 days into an oral regimen of 100 mg phenylbutazone three times a day, was investigated in three volunteers using a stereospecific h.p.l.c. fluorescent assay. The mean elimination half-life of S-warfarin was increased from 25 to 46 h during phenylbutazone administration, whilst that of the R-isomer was decreased from 37 to 25 h. The peak unbound concentrations of both warfarin enantiomers were higher during phenylbutazone administration, due to displacement. Displacement was not stereoselective. The unbound clearance of more potent S-warfarin is decreased by four-fold during phenylbutazone administration, due to substantial inhibition of both 6- and 7-hydroxylation, significant pathways of elimination of S-warfarin in the absence of phenylbutazone. The unbound clearance of R-warfarin is almost unchanged during phenylbutazone administration, due to the marginal effect of phenylbutazone on 6- and 7-hydroxylation, themselves minor pathways of elimination of this enantiomer in the absence of phenylbutazone. The stereoselective reduction of S- and R-warfarin, to their respective SS and RS-alcohols, is also substantially inhibited during phenylbutazone administration. Collectively the data point to the complex effect of phenylbutazone administration on warfarin's pharmacokinetics." @default.
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- W1994237400 date "1983-12-01" @default.
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- W1994237400 title "Phenylbutazone-warfarin interaction in man: further stereochemical and metabolic considerations." @default.
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- W1994237400 doi "https://doi.org/10.1111/j.1365-2125.1983.tb02239.x" @default.
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