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Vitamin K1 in oral solution or tablets: a crossover trial and two randomized controlled trials to compare effects
Author(s) -
Rein N.,
Gebuis E. P. A.,
Lijfering W. M.,
Groeneveld J. J. E.,
Horst F. A. L.,
Cessie S.,
Rosendaal F. R.,
Meer F. J. M.
Publication year - 2014
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12753
Subject(s) - bioavailability , medicine , confidence interval , crossover study , randomized controlled trial , phenprocoumon , vitamin , clinical endpoint , gastroenterology , pharmacology , placebo , warfarin , alternative medicine , pathology , atrial fibrillation
Summary Background Vitamin K1 ( VK 1) reverses the effects of vitamin K antagonists ( VKA s). The literature shows that the bioavailability from solutions might be higher than that from tablets, possibly resulting in different effects. Objectives To compare the bioavailability and effect on the International Normalized Ratio ( INR ) of 5‐mg VK 1 tablets and solution in three randomized clinical trials. Methods and results The bioavailability was determined in a crossover trial with 25 healthy volunteers. VK 1 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 VK 1 concentrations were similar (tablets, 3.2 μg L −1 ; solution, 3.4 μg L −1 ; P = 0.99) after 24 h. Conclusions VK 1 tablets are at least as clinically effective as the solution in countering VKA s.