ISSN:
1573-8744
Keywords:
warfarin
;
warfarin enantiomers
;
serum protein binding
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The protein binding of racemic 14 C-warfarin and 3 H-S(-)-warfarin was determined in individual undiluted serum samples from 31 human subjects and 11 rats. The free fraction value of the R(+) enantiomer was determined indirectly from the free fraction values of the S(−) enantiomer and racemic warfarin, a method which was verified by direct determination of the free fraction of R(+)-warfarin with the unlabeled compound at higher concentrations. The ratio (mean± sd)of free fraction values, R(+):S(−), was 1.32±0.256in man and 1.56±0.351 in the rat;the difference between species is statistically significant (p〈0.025).This ratio was independent of the free fraction value of either enantiomer even though there were pronounced intersubject differences in serum protein binding of the anticoagulant. S(−)-Warfarin is eliminated more rapidly than the R(+) enantiomer in man, while the opposite occurs in rats. The results of this study rule out a species difference in serum protein binding as a factor contributing to the difference in elimination kinetics but help to explain the strong correlation in the elimination kinetics of the two enantiomers in individual rats.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01066216
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