薬理と治療

Abstract

Background The standard formula tablets of warfarin potassium are hygroscopic and fragile. To improve these properties, we have developed tablets with new formulations. The bioequivalence of the new formula tablets was verified against the standard tablets. Methods Single oral doses of 0.5, 1 and 5 mg warfarin potassium tablets of either the new or the standard formula were given to 24 healthy adult volunteers under fasting conditions with a cross−over protocol. The geometric mean ratios for Cmax and AUC0−144 and their 90％ confidence intervals for the new tablets over the standard ones were calculated. Results The 90％ confidence intervals of the geometric mean ratios for Cmax and AUC0−144 obtained from 0.5, 1 and 5 mg tablets were within the range of 0.80−1.25 indicating bioequivalence of all dosages of new formula tablets. Linear relationships were observed between dose vs Cmax and dose vs AUC0−144. No serious adverse events were seen throughout the studies. Conclusions Because all the 0.5, 1 and 5 mg warfarin potassium tablets of new formula are bioequivalent to those of the standard formula, they can be replaced safely with the standard ones.（Jpn Pharmacol Ther 2008；36：401−9）KEY WORDS Warfarin，Bioequivalence study，Formulation，Pharmacokinetics