No Effect of Terodiline on Anticoagulation Effect of Warfarin and Steady-State Plasma Levels of Warfarin Enantiomers in Healthy Volunteers

The influence of terodiline (25 mg b.i.d.) on the anticoagulant effect and plasma levels of warfarin enantiomers was studied in 23 young healthy male volunteers. Racemic warfarin was first given for 24 days to determine the doses required for the subject's vitamin K-dependent coagulation factors to fall within 10-20% of the normal range, as determined by the Thrombotest. During continuous warfarin treatment (mean daily dose 5.3 mg, range 2.5-9.4 mg), terodiline or placebo was given for two weeks in a randomized and double-blind fashion, and then the drugs were crossed over and given for another two weeks. Terodiline did not influence the anticoagulant effect of warfarin or the plasma levels of the warfarin enantiomers. The results indicate that it should not be necessary to monitor patients on combined therapy with terodiline and warfarin more frequently than patients on warfarin monotherapy.