title: Pharmacokinetic and pharmacodynamic variations of acenocoumarol orally administrated either once or twice daily in patients with deep venous thrombosis.
abstract: The literature suggests that variations in anticoagulant effect occur when acenocoumarol is administrated in a daily dose. We assessed the anticoagulant 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 at 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 were noted for INR, factor X and protein C in the two groups (P > 0.10). Nycthemeral significant variation in factor VII when acenocoumarol was administered once daily was noted (P = 0.02), but the clinical relevance of factor VII variation at steady-state is uncertain. In spite of the short pharmacokinetic half-life of acenocoumarol, a stable nycthemeral pharmacodynamic activity was observed after once daily administration; twice-daily administration of acenocoumarol does not appear to be justified.
authors.affiliation: Unité de Pharmacologie Clinique, CHU Saint-Etienne Bellevue, France.
authors.forename: P
authors.initials: P
authors.lastname: Mismetti
authors.forename: J
authors.initials: J
authors.lastname: Reynaud
authors.forename: S
authors.initials: S
authors.lastname: Laporte-Simitsidis
authors.forename: H
authors.initials: H
authors.lastname: Thijssen
authors.forename: B
authors.initials: B
authors.lastname: Tardy-Poncet
authors.forename: B
authors.initials: B
authors.lastname: Tardy
authors.forename: A
authors.initials: A
authors.lastname: Buchmuller
authors.forename: H
authors.initials: H
authors.lastname: Decousus
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D020246:Venous Thrombosis / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; D000074:Acenocoumarol