The Bioavailability of a Mixed Micellar Preparation of Vitamin K1, and its Procoagulant Effect in Anticoagulated Rabbits

Abstract

Abstract We have investigated the pharmacokinetics and procoagulant activity of a new, mixed-micellar preparation of vitamin K1 (MM-K) in male New Zealand White rabbits. Oral administration of MM-K alone caused a significant (P<0·01) increase in the plasma concentrations of vitamin K1 as measured by normal-phase high-performance liquid chromatography (HPLC). Maximum plasma concentrations of vitamin K1 (450 ng mL−1, range 133–824 ng mL−1) were recorded at 3·3 h (range 3–5 h), and were significantly (P < 0·05) greater than those seen after administration of an existing polyethoxylated castor oil preparation (PE-K; Konakion), which were 260 ng mL−1, range 198–390 ng mL−1 (tmax 0·8 h, range 0·4-1·2 h). AUC after MM-K (4·6 μg mL−1 h−1, range 2·1–6·3 μg mL−1) was also significantly (P < 0·05) greater than after PE-K; (1·6 μg mL−1 h−1, range 1·0–2·1 μg mL−1 h−1). However, the bioavailability of vitamin K1 after administration of MM-K was poor (9·4%), and there was considerable intra-individual variability between the concentrations of vitamin K1 recorded in the plasma samples. Both preparations of vitamin K1 stimulated clotting factor synthesis in rabbits anticoagulated with the potent and long-acting coumarin, brodifacoum. Maximum stimulation of clotting factor synthesis by vitamin K1 after MM-K was 87%, range 44–124% (%PCA). The maximum was seen later (tmax 12 h) than after PE-K (PCA 82%, range 47–125%; tmax 5 h). However, there was considerable intra-individual variability in response to both MM-K and PE-K. Furthermore, there was no difference between the maximum PCA produced by the two preparations. It is concluded that the incorporation of vitamin K1 into bile salt micelles does not enhance either the absorption or efficacy of the vitamin after oral administration.