Multiple doses of trandolapril do not affect warfarin pharmacodynamics

The effects of multiple doses of trandolapril (a new angiotensin-converting enzyme inhibitor) on the pharmacodynamics of a single 25 mg dose of warfarin were investigated in 19 men.

A double-blind, placebo-controlled cross-over design was used. The study consisted of two periods of 13 days each, during which subjects received either trandolapril 2 mg or placebo once daily according to a randomisation plan. Warfarin was given on day 8 of each of these periods.

The study was carried out at the Hoechst Research Centre for Clinical Pharmacology, Department of Pharmacology, University of the Orange Free State, Bloemfontein.

Nineteen healthy white men aged between 18 and 28 years and weighing between 65 and 98 kg volunteered for the study.

Prothrombin time (PT) and coagulation factors 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 combinations were also compared at each measuring time.

The point estimate for the ratio of the treatment means of warfarin + trandolapril relative to warfarin + placebo for PT was 97% (90% confidence interval: 90%-103%). The corresponding value for factor VII was 97% (90% confidence interval: 91%-102%).

The concomitant administration of trandolapril did not affect the pharmacodynamic effects of warfarin.