[Interaction of warfarin and vitamin K2 on arterial thrombotic tendency using a rat aorta loop model].
Vitamin K2(K2), a therapeutic agent osteoporosis, is prohibited for patients with thrombosis who are receiving warfarin (WF). However, because some aged patients with thrombosis have osteoporosis, some patients treated with WF may be administered K2 concomitantly. We investigated here the interaction between K2 and WF on thrombosis in a rat aorta loop model. Administration of WF at 0.58, 0.82 and 1.16 mg/l in drinking water for 7 days decreased the thrombotic rate and increased the death rate, dose-dependently. Therefore in the following study, 0.80 mg/l of WF was used. After 2 days of WF-treatment, 1.5, 14 and 145 mg/kg of K2 was administered for 5 days. The blood coagulation time was markedly prolonged by WF treatment for 7 days and this effect was completely inhibited by all doses of K2. WF treatment significantly decreased the cumulative thrombotic rate for 5 days. Administration of 1.5 and 14 mg/kg of K2 did not influence the WF effect on thrombosis. The thrombotic rate in the 145 mg/kg K2 group was lower than that in the WF-control group, but similar to that in the WF-untreated group. These findings suggest that high dose of K2 reduces the effect of WF on thrombosis but does not enhance the occurrence of thrombosis more than that without WF treatment.
Hara
K
K
Department of Applied Drug Research, Eisai Co. Ltd., Tokyo, Japan.
Akiyama
Y
Y
Tomiuga
T
T
Kobayashi
M
M
Kawashima
H
H
D000818:Animals; D001018:Aortic Diseases / Q000473:pathology*; D004347:Drug Interactions; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000473:pathology*; D014812:Vitamin K / Q000008:administration & dosage / Q000494:pharmacology*; D014859:Warfarin / Q000008:administration & dosage / Q000494:pharmacology*
D014812:Vitamin K; D014859:Warfarin