title: Vitamin K1 in oral solution or tablets: a crossover trial and two randomized controlled trials to compare effects.
abstract: BACKGROUND
  Vitamin K1 (VK1) reverses the effects of vitamin K antagonists (VKAs). The literature shows that the bioavailability from solutions might be higher than that from tablets, possibly resulting in different effects.
  
  
  OBJECTIVE
  To compare the bioavailability and effect on the International Normalized Ratio (INR) of 5-mg VK1 tablets and solution in three randomized clinical trials.
  
  
  RESULTS
  The bioavailability was determined in a crossover trial with 25 healthy volunteers. VK1 plasma concentrations were assessed at 0, 2, 4, 5, 6, 8, 10 and 24 h, and the area under the curve was higher in the solution group than in the tablet group (mean difference 365 μg L(-1) h, 95% confidence interval [CI] 230-501, P < 0.0001). In the other two trials, the effects of both formulations on the INR were measured at 0, 24 and 48 h. In the second trial, on 72 patients on phenprocoumon with planned invasive procedures, both formulations were similarly effective, because all patients reached an INR of < 2.0, which was the primary endpoint. In the last trial, on 72 patients on phenprocoumon with an INR of 7.0-11.0, the INR decreased slightly more in the solution group (4.7, 95% CI 4.3-5.1) than in the tablet group (4.2, 95% CI 3.8-4.6). The solution group had a 3.3-fold increased likelihood (95% CI 0.7-15.1) of reaching an INR of < 2.0 at 48 h. Additionally, the increases in VK1 concentrations were similar (tablets, 3.2 μg L(-1) ; solution, 3.4 μg L(-1) ; P = 0.99) after 24 h.
  
  
  CONCLUSIONS
  VK1 tablets are at least as clinically effective as the solution in countering VKAs.
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: van Rein
authors.forename: E P A
authors.initials: EP
authors.lastname: Gebuis
authors.forename: W M
authors.initials: WM
authors.lastname: Lijfering
authors.forename: J J E
authors.initials: JJ
authors.lastname: Groeneveld
authors.forename: F A L
authors.initials: FA
authors.lastname: van der Horst
authors.forename: S
authors.initials: S
authors.lastname: le Cessie
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: F J M
authors.initials: FJ
authors.lastname: van der Meer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D019934:International Normalized Ratio; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D010644:Phenprocoumon / Q000008:administration & dosage; D013607:Tablets; D020246:Venous Thrombosis / Q000188:drug therapy; D010837:Vitamin K 1 / Q000008:administration & dosage* / Q000097:blood*
chemical_list: D000933:Antifibrinolytic Agents; D013607:Tablets; D010837:Vitamin K 1; D010644:Phenprocoumon
keywords: anticoagulants; pharmacokinetics; pharmacology; randomized controlled trial; vitamin K1