Comparison of intestinal absorption of vitamin K2 (menaquinone) homologues and their effects on blood coagulation in rats with hypoprothrombinaemia.
To examine the physiological activities of vitamin K2 (menaquinone, MK) homologues with different numbers of isoprene units, MK with 1-14 isoprene units and menadione (MK-0) were administered to rats with hypoprothrombinaemia, and the absorption, concentration in liver and ameliorating effect of these MK on hypoprothrombinaemia were compared. Hypoprothrombinaemia was induced by giving a vitamin K-deficient diet and warfarin (0.06 mg/kg body weight) for 8 days. Before MK treatment, the MK were undetectable in plasma and liver. At 6 hr after oral MK administration (0.1 mg/kg): MK was not detected in the plasma in rats treated with MK with 1, 2, 3 or more than 12 isoprene units; the MK level in the liver was increased but blood coagulation activity was not improved in rats treated with MK with 0, 9, 10 or 11 isoprene units; the MK level in the liver was increased and hypoprothrombinaemia was slightly improved in rats treated with MK with 7 or 8 isoprene units; and the MK level in the liver was increased and hypoprothrombinaemia was markedly improved in rats treated with MK with 4, 5 or 6 isoprene units. Almost identical results were observed 3 hr after intravenous injection of MK with 4, 5 or 6 isoprene units (10 nmol/kg). These findings suggest that the number of isoprene units of MK is an important factor in its absorption and incorporation into the liver and that the ameliorating effect of MK on hypoprothrombinaemia does not parallel their concentrations in the liver.
Akiyama
Y
Y
Department of Drug Research II, Eisai Co. Ltd., Tokyo, Japan.
Hara
K
K
Matsumoto
A
A
Takahashi
S
S
Tajima
T
T
D000284:Administration, Oral; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D007020:Hypoprothrombinemias / Q000097:blood*; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014812:Vitamin K / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology
D014812:Vitamin K