MULTIPLE DOSES OF TRANDOLAPRIL DO NOT AFFECT WARFARIN PHARMACODYNAMICS

Objective. The effects of multiple doses of trandolapril (a new angiot ensin-converting enzyme inhibitor) on the pharmacodynamics of a single 25 mg dose of warfarin were investigated in 19 men. Design. A double- blind, placebo-controlled cross-over design was used. The study consis ted of two periods of 13 days each, during which subjects received eit her trandolapril 2 mg or Placebo once daily according to a randomisati on plan. Warfarin was given on day 8 of each of these periods. Setting . The study was carried out at the Hoechst Research Centre for Clinica l Pharmacology, Department of Pharmacology, University of the Orange F ree State, Bloemfontein. Patients. Nineteen healthy white men aged bet ween 18 and 28 years and weighing between 65 and 98 kg volunteered for the study. Outcome measures. Prothrombin time (PT) and coagulation fa ctors II, VII, IX and X were measured before and sequentially up to 6 days after warfarin administration. Areas under the PT and coagulation factor time curves for warfarin + trandolapril were compared with the corresponding areas for warfarin + placebo. The two treatment combina tions were also compared at each measuring time. Results. The point es timate for the ratio of the treatment means of warfarin + trandolapril relative to warfarin + placebo for PT was 97% (90% confidence interva l: 90% 103%). The corresponding value for factor VII was 97% (90% conf idence interval: 91% - 102%). Conclusion. The concomitant administrati on of trandolapril did not affect the pharmacodynamic effects of warfa rin.