METHOD FOR STUDYING DRUG-WARFARIN INTERACTIONS

The potential effects of extended-release felodipine on the pharmacoki netics and pharmacodynamics of warfarin were studied in a double-blind crossover study in 12 healthy men. Warfarin dosage was adjusted to ac hieve stable subtherapeutic anticoagulation. Subjects were then random ized to receive 2 weeks of treatment with 10 mg extended-release felod ipine or placebo once daily, and warfarin dosage was adjusted if neces sary to maintain stable international normalized ratio. The pharmacoki netics of R-and S-warfarin and the warfarin dose requirement did not d iffer importantly between periods of treatment with felodipine and pla cebo. The design of this study is suitable for general use in the iden tification of possible effects of other drugs on the pharmacokinetics and pharmacodynamics of warfarin. A different approach is needed if th ere is any reason to expect that warfarin may alter the pharmacokineti cs or pharmacodynamics of the test drug.