COMPARISON OF INTESTINAL-ABSORPTION OF VITAMIN-K-2 (MENAQUINONE) HOMOLOGS AND THEIR EFFECTS ON BLOOD-COAGULATION IN RATS WITH HYPOPROTHROMBINEMIA

被引:29
作者
AKIYAMA, Y
HARA, K
MATSUMOTO, A
TAKAHASHI, S
TAJIMA, T
机构
[1] Department of Drug Research II, Eisai Co. Ltd, Bunkyo-ku, Tokyo, 112-88, 4-6-10, Koishikawa
关键词
MENAQUINONE; BLOOD COAGULATION ACTIVITY; ABSORPTION; MK CONCENTRATION IN LIVER; RATS;
D O I
10.1016/0006-2952(94)00531-P
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
To examine the physiological activities of vitamin K-2 (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.
引用
收藏
页码:1801 / 1807
页数:7
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