Robert A. O Reilly1,2
1Departments of Medicine, Santa Clara Valley Medical Center, San lose, and the University of California, San Francisco
2Hematology Research Laboratory, Institute for Medical Research of Santa Clara County, San Jose, San lose and San Francisco, Calif.
Tóm tắt
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.
