OIV‐A‐4

BACKGROUND In a warfarin interaction study, Asian Indian and Chinese subjects received racaemic warfarin to establish baseline pharmacokinetics (PK) and anticoagulation. Previous data have suggested ethnic differences in INR response to warfarin, thus INR and PK were compared post‐hoc. METHODS 8 Asian Indians (31±7 yrs, 70±10 kg) and 8 Chinese (28±3 yrs, 70±7 kg) healthy male subjects initially received a 25mg oral dose of warfarin, with serial sampling for R‐ and S‐warfarin plasma concentrations and INR for up to 144 hr post dose. Subjects were genotyped for CYP2C9. RESULTS All Chinese subjects were wild‐type homozygous for CYP2C9, whilst 3 Indians subjects were heterozygous for *2 or *3. Overall, there were no significant differences between Indian and Chinese subjects for R‐ or S‐warfarin PK ( Table 1). Baseline Vitamin K1 levels ( Table 1) were also similar. Chinese subjects, however, were found to be more sensitive to warfarin anticoagulant effect, with higher INR AUC and INR max ( Table 1). The 3 CYP2C9 heterozygotes appeared to have higher S‐warfarin exposures as compared to wild‐type subjects. Comparison of Baseline Vit K, PK and INR between Indians and Chinese after 25mg warfarinIndians Chinese Ratio 90% C.I.R‐Warfarin Cmax (ng/ml) 1292 1280 1.01 (0.91–1.11) R‐Warfarin AUC (0‐inf) (ng.h/mL) 106224 95099 1.12 (0.98–1.28) S‐Warfarin Cmax (ng/ml) 1247 1256 0.99 (0.90–1.10) S‐Warfarin AUC (0‐inf) (ng.h/mL) 52328 46894 1.12 (0.86–1.44) INR max 1.64 2.26 0.72 (0.64–0.83) INR AUC 185 227 0.81 (0.74–0.90) Baseline Vitamin K1 (nmol/L) 0.74 0.62 1.20 (0.38–3.83)CONCLUSIONS Despite similar PK profiles and baseline Vitamin K1 levels, Chinese subjects appeared more sensitive to the anticoagulant effect of warfarin. This does not appear to be related to differences in drug metabolism. Clinical Pharmacology & Therapeutics (2005) 79 , P32–P32; doi: 10.1016/j.clpt.2005.12.117