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

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.