The bioavailability of a mixed micellar preparation of vitamin K1, and its procoagulant effect in anticoagulated rabbits.
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 less than 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 less than 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 micrograms mL-1 h-1, range 2.1-6.3 micrograms ML-1 h-1) was also significantly (P less than 0.05) greater than after PE-K (1.6 micrograms mL-1 h-1, range 1.0-2.1 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Winn
M J
MJ
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
White
P M
PM
Scott
A K
AK
Pratt
S K
SK
Park
B K
BK
D015110:4-Hydroxycoumarins / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001682:Biological Availability; D001777:Blood Coagulation / Q000187:drug effects*; D003374:Coumarins / Q000494:pharmacology; D006207:Half-Life; D066298:In Vitro Techniques; D008297:Male; D008823:Micelles; D011817:Rabbits; D010837:Vitamin K 1 / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D003374:Coumarins; D008823:Micelles; C016186:vitamin K1 oxide; D010837:Vitamin K 1; C013418:bromfenacoum