Comparative pharmacokinetics of coumarin anticoagulants XXIX: Elimination kinetics and anticoagulant activity of (S)-(-)-warfarin in rats before and after chronic administration.

The kinetics of elimination and the anticoagulant effect of (S)-(-)-warfarin were determined in adult male rats before and after daily drug administration for 13 days. There was a small but statistically significant (p less than 0.05) decrease in the body clearance of (S)-(-)-warfarin (from 4.84 to 4.37 ml/hr/kg) and an increase in the serum free fraction of racemic warfarin (added to serum in vitro) from 0.00850 to 0.0107 (p less than 0.05). The concentration of (S)-(-)-warfarin in serum at which the synthesis rate of prothrombin complex activity is one-half of the pre-warfarin rate increased from 0.532 to 0.655 microgram/ml on the average (p less than 0.05).