Pharmacokinetics of warfarin enantiomers: a search for intrasubject correlations.
The total body clearance of single doses of R(+)-, S(-)-, and racemic warfarin and the plasma concentration-anticoagulant effect curves for these drugs were determined in 10 healthy men, 21 to 51 yr old. This information was used to calculate the steady-state dose required to decrease prothrombin complex activity to about 30% of normal. This dose (mean +/- SD in mg/70 kg/day) is 17.8 +/- 9.3 for R(+)-warfarin, 6.63 +/- 2.19 for S(-)-warfarin, and 9.4 +/- 1.7 for racemic warfarin. There is a correlation between the maintenance doses of racemic and S(-)-warfarin (r = 0.89, p less than 0.01) but not between those of racemic and R(+)-warfarin (r = 0.30, NS). According to these calculations, the maintenance dose of racemic warfarin required by an individual patient may be a useful predictor of maintenance dose of S(-)-warfarin which will produce a comparable degree of anticoagulation. No such predictability is evident with respect to R(+)-warfarin. The slopes of the log plasma concentration-anticoagulant effect curves for R(+)-and S(-)-warfarin differ significantly. Therefore, the potency ratio of these enantiomers is dose-and concentration-dependent.
D000328:Adult; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013237:Stereoisomerism; D014859:Warfarin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology
D014859:Warfarin