In vivo aspects of potential stereospecific drug interactions of oral warfarin and rutin in rats

Abstract

Present study was designed to investigate the potential drug interactions between rutin and warfarin in rats. In the single dose study, rats pretreated with oral rutin or CM-cellulose as control, were given a single dose of racemic warfarin (1.5 mg/kg) orally and the rutin regimen continued. In the multiple dose study, rats pretreated with oral warfarin (0.15 mg/kg/day) were given rutin or CM-cellulose as control orally along with the daily warfarin. Blood samples were collected at different intervals over 96 h and 168 h respectively. The S- and R- warfarin in serum were analyzed and plasma prothrombin time was measured. With the single dose of warfarin, recovery from hypoprothrombinaemia was found to be much faster in rutin treatment group compared to control animals. Of both S- and R- warfarin, the elimination half-life and apparent volume of distribution values were significantly reduced with rutin treatment. With multiple doses of warfarin, rutin treatment resulted in higher percentage of normal prothrombin complex activity and lower values of S- warfarin. Rutin treatment showed a trend to increase the steady state clearance, reduce the volume of distribution and elimination half-life, of S- warfarin. These results indicate a potential interaction between rutin and warfarin.