Disposition of warfarin enantiomers and metabolites in patients during multiple dosing with rac-warfarin [see comments]

摘要: 1. The disposition of warfarin enantiomers and metabolites has been studied in 36 patients receiving chronic rac-warfarin therapy, titrated to approximately the same anticoagulant response. 2. A stereoselective h.p.l.c. assay was employed determine concentrations (R)- (S)-warfarin, (R,S)-warfarin alcohol (S)-7-hydroxywarfarin plasma 24 h urine samples. (R)-7-hydroxywarfarin, (S,S)-warfarin (R)-6- (S)-6-hydroxywarfarin were also determined fractions unbound using equilibrium dialysis. 3. Wide variability observed daily dose requirements (mean 6.1 mg; range: 2.5-12 mg), (S)-warfarin (0.48 mg l(-1); 0.11-1.02 l(-1)), (R)-warfarin (0.87 0.29-1.82 (0.31 0.02-0.72 l(-1)) (0.25 0.07-0.37 percentage (0.53%; 0.29%-0.82%) (0.54%; 0.26%-0.96%). 4. mean clearances 7.5 1 day-1 per 70 kg (2.5-22.1) for 3.6 (1.6-8.8) (R)-warfarin. There a significant correlation between estimated formation clearance which accounted much latter.(ABSTRACT TRUNCATED AT 250 WORDS)