Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K-1) in severe acute liver disease

Background/Aims: In patients with severe acute liver dysfunction, i.v. phylloquinone (vitamin K-1) may be given to exclude vitamin K deficiency, rather than impaired hepatic synthesis of coagulation factors alone, as the cause of the coagulopathy. However, there have been no studies of the pharmacokinetics or efficacy of i.v. or oral K-1 in such patients.Methods: 49 adults with severe acute liver disease were randomised double-blind to a single 10 mg dose of i.v. or oral mixed-micellar K-1, or placebo. Serum levels of phylloquinone and undercarboxylated prothrombin (PIVKA-II) were assessed before and after treatment.Results: At admission, 13 patients (27 %) had either low serum K-1 levels or elevated PIVKA-II concentrations, indicative of subclinical vitamin K deficiency. In the 16 patients who received i.v. K-1, there was one (6 %) treatment failure (K-1 rise < 10 ng/ml above baseline), compared with 12 of the 15 (80 %) who received oral K, (P < 0.0001). One patient in the placebo group developed overt vitamin K deficiency.Conclusions: A minority of patients with severe acute liver dysfunction have subclinical vitamin K deficiency at the time of presentation, which is corrected by a single dose of i.v. K-1. The intestinal absorption of mixed-micellar K, is unreliable in adults with severe acute liver dysfunction. (c) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved