Studies on the optical enantiomorphs of warfarin in man

The optieal enantiomorphs of warfarin were studied in 10 normal sub;ects. Eaeh sub;ect was given in separate experiments a single oral dose of R(+) warfarin, S(‐) warfarin, and the racemate, R,S(±) warfarin, in the amount of 1.5 mg of drug per kilogram of body weight. The biologie half‐life for (+) warfarin, (‐) warfarin, and raeemie warfarin was 58 ± 5, 33 ± 4, and 42 ± 2 hours, respeetively, a highly significant differenee (p < 0.01) between the enantiomorphs. The blood level of drug for (+) warfarin was 94% greater than that tor (‐) warfarin. The area under the pro thrombin time curve plotted logarithmically showed a 76% greater effect for (‐) warfarin than for (+) warfarin. Thus, the intrinsic activity of (‐) warfarin was 3.4 times as great as thot of (+) warfarin in the induction of hypoprothrombinemia. A high degree of direct correlation was found between the area for the blood level of drug and the hypoprothrombinemic effect for both the (+) and (‐) warfarin enantiomorphs. It is concluded that the greater intrinsic activity of (‐) warfarin than (+) warfarin does not result primarily from the blood level of the enantiomorphs but may result from a difference in permeability or affinity for the receptor site.