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

Abstract

In patients with severe acute liver dysfunction, i.v. phylloquinone (vitamin K1) 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 K1 in such patients. 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. At admission, 13 patients (27%) had either low serum K1 levels or elevated PIVKA-II concentrations, indicative of subclinical vitamin K deficiency. In the 16 patients who received i.v. K1, there was one (6%) treatment failure (K1 rise <10 ng/ml above baseline), compared with 12 of the 15 (80%) who received oral K1 (P<0.0001). One patient in the placebo group developed overt vitamin K deficiency. 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. K1. The intestinal absorption of mixed-micellar K1 is unreliable in adults with severe acute liver dysfunction.