PHARMACOKINETIC AND PHARMACODYNAMIC VARIATIONS OF ACENOCOUMAROL ORALLY ADMINISTRATED EITHER ONCE OR TWICE-DAILY IN PATIENTS WITH DEEP VENOUS THROMBOSIS

The literature suggests that variations in anticoagulant effect occur when acenocoumarol is administrated in a daily dose. We assessed the a nticoagulant effects of acenocoumarol with INR, factors VII and X and protein C in 12 randomly selected hospitalised patients with deep-vein thrombosis, six of them receiving a daily dose of acenocoumarol, the other six receiving twice-daily doses. When the drug effect had been a t a steady-state for at least 72 h, five blood samples were drawn per patient over a period of 24 h. No nycthemeral significant variations w ere noted for INR, factor X and protein C in the two groups (P > 0.10) . Nycthemeral significant variation in factor VII when acenocoumarol w as administered once daily was noted (P = 0.02), but the clinical rele vance of factor VII variation at steady-state is uncertain. In spite o f the short pharmacokinetic half-life of acenocoumarol, a stable nycth emeral pharmacodynamic activity was observed after once daily administ ration; twice-daily administration of acenocoumarol does not appear to be justified. (C) Elsevier, Paris.